HIV antigens and MHC complexes

Abstract

To provide a therapeutic or prophylactic vaccine for HIV disease.SOLUTION: A composition for delivering an antigen-expression system is provided, wherein the antigen-expression system comprises a vector backbone comprising a chimpanzee adenovirus vector, which is optionally a ChAdV68 vector, or an alphavirus vector, which is optionally a Venezuelan equine encephalitis virus vector, wherein the vector backbone comprises at least one HIV MHC class I antigen-encoding nucleotide sequence comprising an MHC class I epitope-encoding nucleotide sequence, wherein optionally the MHC class I epitope-encoding nucleotide sequence encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the specified sequences.SELECTED DRAWING: Figure 34

Description

[Technical Field]

[0001] cross reference This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 869,877, filed July 2, 2019, and U.S. Provisional Patent Application No. 63 / 029,981, filed May 26, 2020, the disclosures of each of which are incorporated herein by reference in their entirety for all purposes.

[0002] Sequence Listing This application has been submitted electronically in ASCII format and contains a Sequence Listing, which is incorporated herein by reference in its entirety. The ASCII copy was created on June 29, 2020, is named GSO-034WO_SL.txt, and is 5,642,000 bytes in size. [Background technology]

[0003] Infectious diseases such as human immunodeficiency virus (HIV) remain difficult to prevent, treat, and / or cure. Although therapeutic vaccines show promise, no therapeutic effect has been achieved for diseases such as HIV that can be used as a therapeutic or preventative vaccine in the population.

[0004] One of the challenges in vaccine design is how to identify and include the "best" therapeutic antigens to elicit anti-HIV responses. Existing methods for identifying and predicting antigen presentation have achieved low positive predictive values ​​(PPV), posing a major obstacle to vaccine design. If a vaccine is designed using a low PPV prediction, it is unlikely that most patients will receive the therapeutic antigen, and even fewer will receive multiple therapeutic antigens (even if all presented peptides are assumed to be immunogenic). Therefore, antigen vaccination using current methods is unlikely to prevent infection with infectious diseases.

[0005] In addition to the challenges of current antigen prediction methods, existing vector systems that can be used for antigen delivery in humans, many of which are of human origin, also present certain challenges. For example, many humans have pre-existing immunity to human viruses as a result of previous natural exposure, and this immunity can pose a significant obstacle to the use of recombinant human viruses to deliver antigens for the treatment of infectious diseases. Summary of the Invention

[0006] Provided herein are compositions for delivering an antigen expression system, the antigen expression system comprising a vector backbone, optionally comprising a chimpanzee adenovirus vector that is a ChAdV68 vector, or an alphavirus vector that is optionally a Venezuelan equine encephalitis virus vector, wherein the vector backbone comprises at least one HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope-encoding nucleic acid sequence, optionally wherein the MHC class I epitope-encoding nucleic acid sequence encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349. In various embodiments, the at least one HIV epitope is selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. In various embodiments, the antigen expression system comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349. In various embodiments, each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence that encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

[0007] Further disclosed herein are compositions for delivering one or more antigens, the compositions comprising one or more HIV MHC class I antigens or one or more nucleic acid sequences encoding one or more HIV MHC class I antigens, each HIV MHC class I antigen comprising an MHC class I epitope, including at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349. In various embodiments, the at least one HIV epitope is selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. In various embodiments, the composition comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigens, each HIV MHC class I antigen comprising an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349. In various embodiments, each HIV MHC class I antigen comprises an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

[0008] In various embodiments, the MHC class I epitopes are selected by: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing the peptide sequences of each of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens is presented by one or more of the MHC proteins, wherein the set of numerical likelihoods is determined based at least on the received mass spectrometry data; and (c) selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens used to generate the MHC class I epitopes.

[0009] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, wherein the one or more vectors comprise: (a) a vector backbone comprising: (i) at least one promoter nucleotide sequence; and (ii) at least one polyadenylation (poly(A)) sequence; (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least one HIV MHC class I antigen-encoding nucleic acid sequence, wherein: (A) an MHC class I epitope-encoding nucleic acid sequence encodes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325-22349; (B) optionally, a 5' linker sequence; and (C) optionally, a 3' linker sequence. Disclosed is a composition comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 57) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0010] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325-2165, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 58) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0011] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 2166-4106, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 59) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0012] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 4107-6241, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 60) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0013] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 6242-8389, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 61) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0014] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 8930-10626, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 62) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0015] 1. A composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising: (i) at least one promoter nucleotide sequence; and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, the antigen cassette comprising: (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 10627-12810, each of the HIV MHC class I antigen-encoding nucleic acid sequences further comprising: (A) optionally a 5' linker sequence; and (B) optionally a 3' linker sequence. Disclosed are compositions comprising: an antigen cassette comprising at least one antigen-encoding nucleic acid sequence, including an MHC class I antigen-encoding nucleic acid sequence; (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 63) amino acid linker sequence; and (v) optionally, at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0016] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 12811-15079; Disclosed is a composition comprising an antigen cassette, wherein each of the MHC class I antigen-encoding nucleic acid sequences comprises: (A) at least one antigen-encoding nucleic acid sequence comprising an HIV MHC class I antigen-encoding nucleic acid sequence, optionally further comprising a 5' linker sequence and (B) optionally a 3' linker sequence; (ii) optionally a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 64) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0017] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 15080-17174; Disclosed is a composition comprising: an antigen cassette, wherein each of the MHC class I antigen-encoding nucleic acid sequences comprises: (A) at least one antigen-encoding nucleic acid sequence comprising an HIV MHC class I antigen-encoding nucleic acid sequence, optionally further comprising a 5' linker sequence; and (B) optionally a 3' linker sequence; (ii) optionally a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 65) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0018] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 17175-19388; Disclosed is a composition comprising an antigen cassette, each of the MHC class I antigen-encoding nucleic acid sequences comprising: (A) at least one antigen-encoding nucleic acid sequence comprising an HIV MHC class I antigen-encoding nucleic acid sequence, optionally further comprising a 5' linker sequence and (B) optionally a 3' linker sequence; (ii) optionally a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 66) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0019] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 19389-21003; Disclosed is a composition comprising an antigen cassette, wherein each of the MHC class I antigen-encoding nucleic acid sequences comprises: (A) at least one antigen-encoding nucleic acid sequence comprising an HIV MHC class I antigen-encoding nucleic acid sequence, optionally further comprising a 5' linker sequence and (B) optionally a 3' linker sequence; (ii) optionally a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 67) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0020] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising (i) at least one promoter nucleotide sequence and (ii) at least one polyadenylation (poly(A)) sequence; and (b) an antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 21004-22349; Disclosed is a composition comprising an antigen cassette, each of the MHC class I antigen-encoding nucleic acid sequences comprising: (A) at least one antigen-encoding nucleic acid sequence comprising an HIV MHC class I antigen-encoding nucleic acid sequence, optionally further comprising a 5' linker sequence and (B) optionally a 3' linker sequence; (ii) optionally a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; (iv) optionally at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 68) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which is a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone.

[0021] Further provided herein is a composition for delivering an antigen expression system comprising one or more vectors, the one or more vectors comprising: (a) a vector backbone comprising: (i) a chimpanzee adenovirus vector, which is optionally a ChAdV68 vector, or an alphavirus vector, which is optionally a Venezuelan equine encephalitis virus vector; (ii) a 26S promoter nucleotide sequence; and (iii) a polyadenylation (poly(A)) sequence; and (b) an antigen cassette integrated between the 26S promoter nucleotide sequence and the poly(A) sequence, the antigen cassette comprising: (i) at least one antigen-encoding nucleic acid sequence, which comprises: (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV 1 antigens linearly linked to each other. MHC class I antigen-encoding nucleic acid sequences, each comprising: (A) an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope having a length of 7 to 15 amino acids, wherein at least one of the MHC class I epitopes is selected from the group consisting of the epitope sequences of any one of SEQ ID NOs: 325 to 22349; (B) a 5' linker sequence encoding a natural N-terminal nucleic acid sequence of the MHC class I epitope, encoding a peptide having a length of at least 3 amino acids; and (C) an MHC class I epitope-encoding nucleic acid sequence encoding a peptide having a length of at least 3 amino acids. and a 3' linker sequence encoding a peptide that is at least 3 amino acids in length, wherein the antigen cassette is operably linked to a 26S promoter nucleotide sequence, each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide that is 13 to 25 amino acids in length, and the 3' end of each MHC class I antigen-encoding nucleic acid sequence except for the last MHC class I antigen-encoding nucleic acid sequence in the antigen cassette is linked to the 5' end of the subsequent MHC class I antigen-encoding nucleic acid sequence; and (ii) at least two MHC class II antigen-encoding nucleic acid sequences, (I) a PADRE MHC class II sequence, (II) a tetanus toxoid MHC class II sequence, and (III) a PADRE MHC class II sequence.and an antigen cassette comprising at least two MHC class II antigen-encoding nucleic acid sequences, the at least two MHC class II antigen-encoding nucleic acid sequences comprising: (IV) a first nucleic acid sequence encoding a GGPPG (SEQ ID NO: 69) amino acid linker sequence linking the MHC class II sequence and the tetanus toxoid MHC class II sequence; (IV) a second nucleic acid sequence encoding a GGPPG (SEQ ID NO: 70) amino acid linker sequence linking the 5' ends of the at least two MHC class II antigen-encoding nucleic acid sequences to an HIV MHC class I antigen-encoding nucleic acid sequence; and (V) optionally, a third nucleic acid sequence encoding a GGPPG (SEQ ID NO: 71) amino acid linker sequence at the 3' ends of the at least two MHC class II antigen-encoding nucleic acid sequences.

[0022] In various embodiments, the ordered sequence of each element of the antigen cassette is, from 5' to 3', as follows: P a -(L5 b -N c -L3 d ) X -(G5 e -U f ) Y -G3 g wherein P comprises a second promoter nucleotide sequence, wherein a=0 or 1; N comprises one of an MHC class I epitope-encoding nucleic acid sequence, wherein c=1; L5 comprises a 5' linker sequence, wherein b=0 or 1; L3 comprises a 3' linker sequence, wherein d=0 or 1; G5 comprises one of at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 72) amino acid linker, wherein e=0 or 1; G3 comprises one of at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 73) amino acid linker, wherein g=0 or 1; U comprises one of said at least one MHC class II antigen-encoding nucleic acid sequence, wherein f=1; X=1 to 400; and wherein for each X, a corresponding N c is an epitope-encoding nucleic acid sequence, and Y=0, 1, or 2, where for each Y, the corresponding U f is an antigen-encoding nucleic acid sequence].

[0023] In various embodiments, for each X, a corresponding N c are different MHC class I epitope-encoding nucleic acid sequences. In various embodiments, for each Y, a corresponding U f are different MHC class II antigen-encoding nucleic acid sequences.

[0024] In various embodiments, a=0, b=1, d=1, e=1, g=1, h=1, X=20, Y=2, the at least one promoter nucleotide sequence is a single 26S promoter nucleotide sequence provided by the backbone, the at least one polyadenylation poly(A) sequence is a poly(A) sequence of at least 100 consecutive A nucleotides provided by the backbone (SEQ ID NO: 74), each N encodes an MHC class I epitope 7-15 amino acids in length, L5 is a native 5' linker sequence encoding the native N-terminal amino acid sequence of an MHC I epitope, the 5' linker sequence encodes a peptide that is at least 3 amino acids in length, and L3 is a native 5' linker sequence encoding the native N-terminal amino acid sequence of an MHC I epitope, the 5' linker sequence encodes a peptide that is at least 3 amino acids in length, and L4 is a native 5' linker sequence encoding the native N-terminal amino acid sequence of an MHC I epitope 7-15 amino acids in length. and U is a natural 3' linker sequence encoding a natural terminal nucleic acid sequence of an MHC Class I epitope, wherein the 3' linker sequence encodes a peptide that is at least 3 amino acids in length; U is each of a PADRE class II sequence and a tetanus toxoid MHC Class II sequence; (a) the vector backbone comprises a chimpanzee adenovirus vector that is a ChAdV68 vector, or optionally an alphavirus vector that is a Venezuelan equine encephalitis virus vector, and each of the MHC Class I antigen-encoding nucleic acid sequences encodes a polypeptide that is 13 to 25 amino acids in length.

[0025] In various embodiments, the composition further comprises a nanoparticulate delivery vehicle. In various embodiments, the nanoparticulate delivery vehicle is a lipid nanoparticle (LNP). In various embodiments, the LNP comprises an ionizable amino lipid. In various embodiments, the ionizable amino lipid comprises an MC3-like (dilinoleylmethyl-4-dimethylaminobutyrate) molecule. In various embodiments, the nanoparticle delivery vehicle encapsulates an antigen expression system. In various embodiments, the antigen cassette is incorporated between at least one promoter nucleotide sequence and at least one poly(A) sequence. In various embodiments, the at least one promoter nucleotide sequence is operably linked to the antigen-encoding nucleic acid sequence. In various embodiments, the one or more vectors comprise one or more positive-strand RNA vectors. In various embodiments, the one or more positive-strand RNA vectors have a 5'7-methylguanosine (m7G) cap. In various embodiments, the one or more positive-strand RNA vectors are generated by in vitro transcription. In various embodiments, the one or more vectors are autonomously replicating within mammalian cells. In various embodiments, the backbone comprises at least one nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus. In various embodiments, the backbone comprises at least one nucleotide sequence of Venezuelan equine encephalitis virus. In various embodiments, the backbone comprises at least a sequence for nonstructural protein-mediated amplification, a 26S promoter sequence, a poly(A) sequence, a nonstructural protein 1 (nsP1) gene, a nsP2 gene, a nsP3 gene, and a nsP4 gene encoded by a nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus.In various embodiments, the backbone includes at least a sequence for nonstructural protein-mediated amplification encoded by a nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus, a 26S promoter sequence, and a poly(A) sequence.

[0026] In various embodiments, the sequence for nonstructural protein-mediated amplification is selected from the group consisting of an alphavirus 5' UTR, a 51 nt CSE, a 24 nt CSE, a 26S subgenomic promoter sequence, a 19 nt CSE, an alphavirus 3' UTR, or a combination thereof. In various embodiments, the backbone does not encode the structural virion proteins capsid E2 and E1. In various embodiments, the antigen cassette is inserted in place of a structural virion protein within the nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus. In various embodiments, the Venezuelan equine encephalitis virus comprises the sequence of SEQ ID NO:3 or SEQ ID NO:5. In various embodiments, the Venezuelan equine encephalitis virus further comprises the sequence of SEQ ID NO:3 or SEQ ID NO:5 with a deletion between base pairs 7544 and 11175. In various embodiments, the backbone comprises the sequence set forth in SEQ ID NO:6 or SEQ ID NO:7.

[0027] In various embodiments, the antigen cassette is inserted at position 7544 to replace the deletion between base pairs 7544 and 11175 set forth in SEQ ID NO:3 or SEQ ID NO:5. In various embodiments, insertion of the antigen cassette results in transcription of a polycistronic RNA comprising the nsP1-4 genes and at least one antigen-encoding nucleic acid sequence, wherein the nsP1-4 genes and the at least one antigen-encoding nucleic acid sequence are in separate open reading frames. In various embodiments, the backbone comprises at least one nucleotide sequence of a chimpanzee adenoviral vector. In various embodiments, the chimpanzee adenoviral vector is a ChAdV68 vector. In various embodiments, the at least one promoter nucleotide sequence is a native 26S promoter nucleotide sequence encoded by the backbone. In various embodiments, the at least one promoter nucleotide sequence is an exogenous RNA promoter. In various embodiments, the second promoter nucleotide sequence is a 26S promoter nucleotide sequence. In various embodiments, the second promoter nucleotide sequence comprises multiple 26S promoter nucleotide sequences, each 26S promoter nucleotide sequence directing transcription of one or more of the separate open reading frames. In various embodiments, the one or more vectors are each at least 300 nt in size.

[0028] In various embodiments, the one or more vectors are each at least 1 kb in size. In various embodiments, the one or more vectors are each 2 kb in size. In various embodiments, the one or more vectors are each less than 5 kb in size. In various embodiments, at least one of the at least one antigen-encoding nucleic acid sequence encodes a polypeptide sequence or a portion thereof presented by an MHC class I protein. In various embodiments, the antigen-encoding nucleic acid sequences are directly linked to each other. In various embodiments, at least one of the at least one antigen-encoding nucleic acid sequence is linked to a different antigen-encoding nucleic acid sequence by a nucleic acid sequence encoding a linker. In various embodiments, the linker links two MHC class I epitope sequences or one MHC class I epitope sequence to one MHC class II sequence. In various embodiments, the linker is selected from the group consisting of: (1) a stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive glycine residues (SEQ ID NO: 75), (2) a stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive alanine residues (SEQ ID NO: 76), (3) two arginine residues (RR), (4) alanine, alanine, tyrosine (AAY), (5) a consensus sequence at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues in length that is efficiently processed by the mammalian proteasome, and (6) one or more naturally occurring sequences adjacent to the antigen from a cognate source protein and at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 2-20 amino acid residues in length. In various embodiments, the linker connects two MHC class II sequences or one MHC class II epitope sequence with one MHC class I sequence. In various embodiments, the linker comprises the sequence GPGPG (SEQ ID NO: 77).In various embodiments, at least one of the at least one antigen-encoding nucleic acid sequences is operably or directly linked to a separate or contiguous sequence that enhances expression, stability, cellular trafficking, processing and presentation, and / or immunogenicity of the at least one antigen-encoding nucleic acid sequence.

[0029] In various embodiments, the separate or contiguous sequences comprise at least one of a ubiquitin sequence, a ubiquitin sequence modified to enhance proteasome targeting (e.g., a ubiquitin sequence containing a Gly→Ala substitution at position 76), an immunoglobulin signal sequence (e.g., IgK), a major histocompatibility class I sequence, a lysosomal-associated membrane protein (LAMP)-1, a human dendritic cell lysosomal-associated membrane protein, and a major histocompatibility class II sequence, optionally wherein the ubiquitin sequence modified to enhance proteasome targeting is A76. In various embodiments, the at least one antigen-encoding nucleic acid sequence comprises at least 2 to 10, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleic acid sequences. In various embodiments, the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 15-20, 11-100, 11-200, 11-300, 11-400, or up to 400 nucleic acid sequences. In various embodiments, the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 2-400 nucleic acid sequences, and at least two of the antigen-encoding nucleic acid sequences encode a polypeptide sequence or a portion thereof presented by an MHC class I protein. In various embodiments, at least two of the antigen-encoding nucleic acid sequences encode a polypeptide sequence or a portion thereof presented by an MHC class I protein.

[0030] In various embodiments, when administered to a subject and translated, at least one of the antigens or at least one of the MHC class I epitopes encoded by the at least one HIV MHC class I antigen-encoding nucleic acid is presented on an antigen-presenting cell, resulting in an immune response. In various embodiments, when the at least one HIV MHC class I antigen-encoding nucleic acid sequence is administered to a subject and translated, at least one of the antigens is presented on an antigen-presenting cell, resulting in an immune response, and optionally, expression of each of the at least one antigen-encoding nucleic acid sequence is driven by at least one promoter nucleotide sequence. In various embodiments, each MHC class I antigen-encoding nucleic acid sequence encodes a polypeptide sequence that is 8 to 35 amino acids in length, optionally 9 to 17, 9 to 25, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 amino acids in length. In various embodiments, there is at least one MHC class II antigen-encoding nucleic acid sequence. In various embodiments, at least one MHC class II antigen-encoding nucleic acid sequence is 12 to 20, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 20 to 40 amino acids in length. In various embodiments, at least one MHC class II antigen-encoding nucleic acid sequence is present and comprises at least one universal MHC class II antigen-encoding nucleic acid sequence, optionally wherein the at least one universal sequence comprises at least one of tetanus toxoid and PADRE. In various embodiments, at least one promoter nucleotide sequence or the second promoter nucleotide sequence is inducible. In various embodiments, at least one promoter nucleotide sequence or the second promoter nucleotide sequence is non-inducible. In various embodiments, at least one poly(A) sequence comprises a poly(A) sequence that is native to the backbone. In various embodiments, at least one poly(A) sequence comprises a poly(A) sequence that is exogenous to the backbone.In various embodiments, at least one poly(A) sequence is operably linked to at least one of the at least one antigen-encoding nucleic acid sequences. In various embodiments, the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides (SEQ ID NO: 78). In various embodiments, the at least one poly(A) sequence is at least 100 consecutive A nucleotides (SEQ ID NO: 79).

[0031] In various embodiments, the antigen expression system further comprises at least one of an intron sequence, a woodchuck hepatitis virus post-transcriptional regulator (WPRE) sequence, an internal ribosome entry sequence (IRES) sequence, a nucleotide sequence encoding a 2A self-cleaving peptide sequence, a nucleotide sequence encoding a furin cleavage site, or a sequence within a 5' or 3' non-coding region known to improve mRNA nuclear transport, stability, or translation efficiency, operably linked to at least one of the at least one antigen-encoding nucleic acid sequence. In various embodiments, the antigen expression system further comprises a reporter gene, including, but not limited to, green fluorescent protein (GFP), a GFP mutant, secreted alkaline phosphatase, luciferase, a luciferase mutant, or a detectable peptide or epitope. In various embodiments, the detectable peptide or epitope is selected from the group consisting of an HA tag, a Flag tag, a His tag, or a V5 tag. In various embodiments, the at least one MHC class I antigen-encoding nucleic acid sequence is selected by performing the following steps: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing the peptide sequences of each of a set of antigens; (b) inputting the peptide sequences of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens is presented by one or more of the MHC allele proteins, wherein the set of numerical likelihoods is determined based at least on the received mass spectrometry data; and (c) selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens used to generate the at least one MHC class I antigen-encoding nucleic acid sequence.

[0032] In various embodiments, each of the MHC class I epitope-encoding nucleic acid sequences is selected by performing the following steps: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing data, where the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens is presented by one or more MHC allele proteins, where the set of numerical likelihoods is determined based at least on the received mass spectrometry data; and (c) selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens used to generate at least 20 MHC class I antigen-encoding nucleic acid sequences. In various embodiments, the number of sets of selected antigens is between 2 and 20. In various embodiments, the presentation model represents a dependency between (a) the existence of a pairing of a particular one of the MHC alleles with a particular amino acid at a particular position in a peptide sequence, and (b) the likelihood of presentation of such a peptide sequence containing said particular amino acid at said particular position by a particular one of the MHC alleles of said pair.

[0033] In various embodiments, selecting the set of selected antigens includes selecting antigens with an increased likelihood of being presented relative to antigens not selected based on the presentation model, where optionally the selected antigens have been validated as being presented by one or more specific MHC alleles. In various embodiments, selecting the set of selected antigens includes selecting antigens with an increased likelihood of being able to induce an immune response in response to the presence of HIV in a subject, relative to antigens not selected based on the presentation model. In various embodiments, selecting the set of selected antigens includes selecting antigens with an increased likelihood of being presented to naive T cells by professional antigen-presenting cells (APCs), relative to antigens not selected based on the presentation model, where optionally the APCs are dendritic cells (DCs). In various embodiments, selecting the set of selected antigens includes selecting antigens with a decreased likelihood of being inhibited by central or peripheral tolerance relative to antigens not selected based on the presentation model. In various embodiments, selecting the set of selected antigens includes selecting antigens with a decreased likelihood of being able to induce an autoimmune response against normal tissue in a subject, relative to antigens not selected based on the presentation model.

[0034] In various embodiments, the exome or transcriptome nucleotide sequencing data is obtained by next-generation sequencing (NGS) or any massively parallel sequencing approach. In various embodiments, the antigen cassette includes a junction epitope sequence formed by adjacent sequences within the antigen cassette. In various embodiments, at least one or each junction epitope sequence has an affinity for MHC greater than 500 nM. In various embodiments, each junction epitope sequence is non-self. In various embodiments, each MHC class I epitope is predicted or verified to be presentable by at least one HLA allele present in at least 5% of the population. In various embodiments, each MHC class I epitope is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA prevalence of at least 0.01% in the population. In various embodiments, each of the MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA abundance in the population of at least 0.1%.

[0035] Further disclosed herein is a pharmaceutical composition comprising the composition described above and a pharmaceutically acceptable carrier. In various embodiments, the composition further comprises an adjuvant.

[0036] Also disclosed herein is an isolated nucleotide sequence or set of isolated nucleotide sequences comprising the antigen cassette of any of the above compositions and one or more elements derived from the sequence of SEQ ID NO:3 or SEQ ID NO:5, wherein optionally the one or more elements are selected from the group consisting of a sequence required for nonstructural protein-mediated amplification, a 26S promoter nucleotide sequence, a poly(A) sequence, and the nsP1-4 genes of the sequence set forth in SEQ ID NO:3 or SEQ ID NO:5, and optionally the nucleotide sequences are cDNA. In various embodiments, the sequence or set of isolated nucleotide sequences comprises the antigen cassette of any of the above compositions inserted at position 7544 of the sequence set forth in SEQ ID NO:6 or SEQ ID NO:7. In various embodiments, the isolated nucleotide sequence further comprises a nucleotide sequence for a T7 or SP6 RNA polymerase promoter located 5' to the one or more elements derived from the sequence of SEQ ID NO:3 or SEQ ID NO:5, and optionally one or more restriction sites located 3' to the poly(A) sequence. In various embodiments, the antigen cassette of any of the above compositions is inserted at position 7563 of SEQ ID NO:8 or SEQ ID NO:9.

[0037] Further disclosed herein is a vector or a set of vectors comprising the above-described nucleotide sequence.Further disclosed herein is an isolated cell comprising the above-described nucleotide sequence or set of isolated nucleotide sequences, optionally wherein the cell is a BHK-21, CHO, HEK293 or mutant thereof, 911, HeLa, A549, LP-293, PER.C6, or AE1-2a cell.

[0038] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject any of the compositions described above or the pharmaceutical composition described above. Also disclosed herein is a method for inducing an immune response in a subject, comprising administering to the subject any of the compositions described above or the pharmaceutical composition described above. In various embodiments, the subject expresses at least one HLA allele predicted or known to present at least one of the MHC class I epitopes encoded by one or more vectors of the antigen expression system. In various embodiments, the composition is administered intramuscularly (IM), intradermally (ID), subcutaneously (SC), or intravenously (IV).

[0039] In various embodiments, the composition is administered intramuscularly. In various embodiments, the method further comprises administering a second vaccine composition to the subject. In various embodiments, the second vaccine composition is administered prior to administration of the composition or pharmaceutical composition. In various embodiments, the second vaccine composition is administered subsequent to administration of the composition or pharmaceutical composition. In various embodiments, the second vaccine composition is the same as the composition or pharmaceutical composition. In various embodiments, the second vaccine composition is different from the composition or pharmaceutical composition. In various embodiments, the second vaccine composition comprises a chimpanzee adenoviral vector encoding at least one antigen-encoding nucleic acid sequence. In various embodiments, the at least one antigen-encoding nucleic acid sequence encoded by the chimpanzee adenoviral vector is the same as at least one antigen-encoding nucleic acid sequence of any of the above compositions.

[0040] Further disclosed herein are methods for producing the antigen expression system described above, comprising: (a) obtaining a linearized DNA sequence comprising a backbone and an antigen cassette; (b) in vitro transcribing the linearized DNA sequence by adding the linearized DNA sequence to an in vitro transcription reaction containing all components necessary for transcribing the linearized DNA sequence into RNA, optionally further comprising in vitro addition of an m7g cap to the resulting RNA; and (c) isolating one or more vectors from the in vitro transcription reaction. In various embodiments, the linearized DNA sequence is generated by linearizing a DNA plasmid sequence or by amplification using PCR. In various embodiments, the DNA plasmid sequence is generated using one of bacterial recombination or total genome DNA synthesis or total genome DNA synthesis involving amplification of DNA synthesized in bacterial cells. In various embodiments, isolating one or more vectors from the in vitro transcription reaction involves one or more of phenol-chloroform extraction, silica column-based purification, or similar RNA purification methods.

[0041] Further disclosed herein are methods of producing a composition for delivering an antigen expression system, the methods comprising: (a) providing components of a nanoparticulate delivery vehicle; (b) providing an antigen expression system; and (c) providing conditions sufficient for the nanoparticulate delivery vehicle and the antigen expression system to produce a composition for delivering the antigen expression system. In various embodiments, such conditions are provided by microfluidic mixing.

[0042] Further provided herein are methods of evaluating a subject with HIV, comprising: a) determining, or having previously determined, the HIV subtype of the subject's HIV; b) determining, or having previously determined, whether the subject expresses an HLA allele predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of the epitope sequences of any one of SEQ ID NOS: 325-22349; and d) optionally administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA allele expressed by the subject is selected from the group consisting of the HLA alleles of Tables 35-45.

[0043] Further provided herein is a method for evaluating a subject having HIV, the method comprising the steps of: a) determining, or having previously determined, that the subject's HIV is HIV subtype A1; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 2165; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 35.

[0044] Further provided herein is a method for evaluating a subject having HIV, the method comprising the steps of: a) determining, or having previously determined, that the subject's HIV is HIV subtype A2; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 2166 to 4106; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 36.

[0045] Further provided herein is a method for evaluating a subject having HIV, the method comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype B; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 4107-6241; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 37.

[0046] Further provided herein is a method for evaluating a subject having HIV, the method comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype C; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 6242 to 8389; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 38.

[0047] Further provided herein is a method of evaluating a subject having HIV, the method comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype D; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 8930 to 10626; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 39.

[0048] Further provided herein are methods of evaluating a subject with HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F1; b) determining, or having previously determined, whether the subject expresses an HLA allele predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and HIV subtype expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 10627-12810; and d) optionally administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA allele expressed by the subject is selected from the group consisting of the HLA alleles in Table 40.

[0049] Further provided herein are methods of evaluating a subject with HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F2; b) determining, or having previously determined, whether the subject expresses an HLA allele predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and HIV subtype expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOS: 12811-15079; and d) optionally administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA allele expressed by the subject is selected from the group consisting of the HLA alleles in Table 41.

[0050] Further provided herein are methods of evaluating a subject with HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype G; b) determining, or having previously determined, whether the subject expresses an HLA allele predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 15080-17174; and d) optionally administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA allele expressed by the subject is selected from the group consisting of the HLA alleles in Table 42.

[0051] Further provided herein is a method for evaluating a subject having HIV, the method comprising the steps of: a) determining, or having previously determined, that the subject's HIV is HIV subtype H; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 17175 to 19388; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 43.

[0052] Further provided herein is a method for evaluating a subject having HIV, the method comprising the steps of: a) determining, or having previously determined, that the subject's HIV is HIV subtype J; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 19389 to 21003; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 44.

[0053] Further provided herein is a method for evaluating a subject having HIV, the method comprising the steps of: a) determining, or having previously determined, that the subject's HIV is HIV subtype K; b) determining, or having previously determined, whether the subject expresses an HLA allele that is predicted or known to present an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with an antigen-based vaccine if the subject expresses an HLA allele and an HIV subtype that expresses an MHC class I epitope encoded by an antigen-encoding nucleic acid sequence in the antigen-based vaccine, wherein the MHC class I epitope comprises at least one MHC class I epitope sequence that includes at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 21004 to 22349; and d) optionally, administering, or having previously administered, the antigen-based vaccine to the subject. In various embodiments, the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles in Table 45.

[0054] In various embodiments, determining or having previously determined the HIV subtype of a subject's HIV comprises obtaining a dataset indicative of the HIV subtype from a third party that processed a sample from the subject. In various embodiments, determining or having previously determined whether a subject expresses an HLA allele comprises obtaining a dataset from a third party that processed a sample from the subject. In various embodiments, determining or having previously determined whether a subject expresses an HLA allele comprises obtaining a sample from the subject and assaying the sample using a method selected from the group consisting of exome sequencing, targeted exome sequencing, transcriptome sequencing, Sanger sequencing, PCR-based genotyping assays, mass spectrometry-based methods, microarrays, nanostrings, ISH, and IHC. In various embodiments, the sample is selected from tissue, body fluid, blood, spinal fluid, or fine needle aspirate. In some aspects, the HLA allele has an HLA frequency of at least 1%.

[0055] Further disclosed herein is a method for treating a subject, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349. Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165.

[0056] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106.

[0057] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241.

[0058] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389.

[0059] Further disclosed herein is a method comprising administering to a subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930-10626.

[0060] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810.

[0061] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811-15079.

[0062] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080-17174.

[0063] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175-19388.

[0064] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389 to 21003.

[0065] Further disclosed herein is a method for treating a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349.

[0066] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349.

[0067] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165.

[0068] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106.

[0069] Further provided herein is a method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: Disclosed are methods comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope, wherein said at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241.

[0070] A method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389. Further disclosed herein is a method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 8930 to 10626.

[0071] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810.

[0072] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811 to 15079.

[0073] Further disclosed herein is a method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope, wherein said at least one MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080 to 17174.

[0074] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175 to 19388.

[0075] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389-21003.

[0076] Further disclosed herein is a method for inducing an immune response in a subject with HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine comprises 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding the at least one MHC class I epitope, wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349.

[0077] In various embodiments, the subject expresses at least one HLA allele predicted or known to present said at least one MHC class I epitope sequence. In various embodiments, the method further includes determining that the subject is a candidate for receiving the antigen-based vaccine prior to administering the antigen-based vaccine to the subject, said determining including 1) determining that the subject expresses an HLA allele known or predicted to present said at least one MHC class I epitope, and 2) identifying that the subject has been exposed to or is susceptible to exposure to an HIV subtype. In various embodiments, the at least one HLA allele is selected from the group consisting of the HLA alleles of Tables 35-45.

[0078] In various embodiments, the antigen-based vaccine comprises an antigen expression system. In various embodiments, the antigen expression system comprises any one of the antigen expression systems described above. In various embodiments, the antigen-based vaccine comprises any one of the pharmaceutical compositions described above.

[0079] In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 325-2165. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 2166-4106. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 4107-6241. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 6242-8389. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 8930-10626. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 10627-12810. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 12811-15079. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 15080-17174. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 17175-19388. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 19389-21003. In various embodiments, each MHC class I epitope comprises a sequence selected from the group consisting of the epitope sequence of any one of SEQ ID NOs: 21004-22349.

[0080] Further disclosed herein is a method of assessing a subject with HIV, comprising: a) determining, or having already been determined, that the subject expresses HLA alleles; b) obtaining, or having already obtained, sequencing data for HIV present in the subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence is selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 325-22349, and a second candidate epitope sequence is a variant epitope sequence, each of the first and second candidate epitope sequences being predicted to be presented by an HLA allele expressed by the subject; d) generating an antigen-based vaccine comprising the selected candidate epitope sequences; and e) optionally administering, or having already administered, the antigen-based vaccine to the subject.

[0081] Further disclosed herein is a method for treating a subject with HIV, comprising: a) determining, or having already been determined, that the subject expresses HLA alleles; b) obtaining, or having already been obtained, sequencing data for HIV present in the subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence is selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 325-22349, and a second candidate epitope sequence is a variant epitope sequence, each of the first and second candidate epitope sequences being predicted to be presented by an HLA allele expressed by the subject; d) generating an antigen-based vaccine comprising the selected candidate epitope sequences; and e) optionally administering, or having already administered, the antigen-based vaccine to the subject. In various embodiments, the epitope sequence of any one of SEQ ID NOS: 325-22349 is identified by applying a display model trained on HLA-presented peptides sequenced by mass spectrometry. In various embodiments, the display model exhibits a precision value of 0.28 at a recall of 40%. In various embodiments, the display model exhibits an AUC of 0.24. [The present invention 1001] 1. A composition for delivering an antigen expression system, the antigen expression system comprising: a vector backbone comprising a chimpanzee adenovirus vector, optionally a ChAdV68 vector, or an alphavirus vector, optionally a Venezuelan equine encephalitis virus vector; wherein the vector backbone comprises at least one HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope-encoding nucleic acid sequence, and optionally the MHC class I epitope-encoding nucleic acid sequence encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349. [The present invention 1002] 1001. The composition of the present invention, wherein said at least one HIV epitope is selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. [The present invention 1003] The composition of claim 1001 or 1002, wherein the antigen expression system comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences, each of which comprises an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349. [The present invention 1004] 1003. The composition of the present invention, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. [The present invention 1005] A composition for delivering one or more antigens, comprising one or more HIV MHC class I antigens or one or more nucleic acid sequences encoding one or more HIV MHC class I antigens, wherein each HIV MHC class I antigen comprises an MHC class I epitope, including at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349. [The present invention 1006] 1005. The composition of the present invention, wherein each HIV MHC class I antigen comprises an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. [The present invention 1007] 1005 or 1006, wherein the composition comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigens, each HIV MHC class I antigen comprising an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349. [The present invention 1008] 1007. The composition of the present invention, wherein each HIV MHC class I antigen comprises an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661. [The present invention 1009] the MHC class I epitope (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens will be presented by one or more of the MHC proteins, said set of numerical likelihoods being determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens used to generate MHC class I epitopes; Any of the compositions of 1001 to 1008 of the present invention, selected by carrying out the above. [The present invention 1010] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least one HIV MHC class I antigen-encoding nucleic acid sequence, (A) an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope including at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 22349; (B) optionally, a 5' linker sequence; (C) optionally, a 3' linker sequence; the at least one HIV MHC class I antigen-encoding nucleic acid sequence comprising: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 151) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1011] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 152) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1012] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 153) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1013] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107 to 6241; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 154) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1014] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 155) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1015] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930 to 10626; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 156) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1016] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627 to 12810; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 157) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1017] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811 to 15079; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 158) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1018] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope selected from the group consisting of any one of the epitope sequences of SEQ ID NOs: 15080 to 17174; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 159) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1019] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175 to 19388; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 160) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1020] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389 to 21003; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 161) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1021] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349; each of said HIV MHC class I antigen-encoding nucleic acid sequences (A) optionally, a 5' linker sequence; (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally, at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 162) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to the vector backbone; The antigen cassette comprising: The composition comprising: [The present invention 1022] 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) a chimpanzee adenovirus vector, which is optionally a ChAdV68 vector, or an alphavirus vector, which is optionally a Venezuelan equine encephalitis virus vector; (ii) a 26S promoter nucleotide sequence; and (iii) a polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette integrated between the 26S promoter nucleotide sequence and the poly(A) sequence, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each of which comprises: (A) an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope having a length of 7 to 15 amino acids, wherein at least one of the MHC class I epitopes is selected from the group consisting of epitope sequences of any one of SEQ ID NOs: 325 to 22349; and (B) a 5' linker sequence encoding the native N-terminal amino acid sequence of the MHC class I epitope, encoding a peptide that is at least 3 amino acids in length; (C) a 3' linker sequence encoding the native C-terminal amino acid sequence of the MHC class I epitope and encoding a peptide that is at least 3 amino acids in length; Including, the HIV MHC class I antigen-encoding nucleic acid sequence, wherein the antigen cassette is operably linked to the 26S promoter nucleotide sequence, each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide having a length of 13 to 25 amino acids, and the 3' end of each MHC class I antigen-encoding nucleic acid sequence except for the last MHC class I antigen-encoding nucleic acid sequence in the antigen cassette is linked to the 5' end of the subsequent MHC class I antigen-encoding nucleic acid sequence; and the at least one antigen-encoding nucleic acid sequence comprising: (ii) at least two MHC class II antigen-encoding nucleic acid sequences, (I) PADRE MHC class II sequence; (II) a tetanus toxoid MHC class II sequence; and (III) a first nucleic acid sequence encoding a GPGPG (SEQ ID NO: 163) amino acid linker sequence that connects the PADRE MHC class II sequence to the tetanus toxoid MHC class II sequence; (IV) a second nucleic acid sequence encoding a GPGPG (SEQ ID NO: 164) amino acid linker sequence that connects the 5' ends of the at least two MHC class II antigen-encoding nucleic acid sequences to the HIV MHC class I antigen-encoding nucleic acid sequence; (V) optionally, a third nucleic acid sequence encoding a GPGPG (SEQ ID NO: 165) amino acid linker sequence at the 3' ends of the at least two MHC class II antigen-encoding nucleic acid sequences; and and the at least two MHC class II antigen-encoding nucleic acid sequences comprising: The antigen cassette comprising: The composition comprising: [The present invention 1023] The ordered sequence of each element of the antigen cassette, from 5' to 3', is as follows: P a -(L5 b -N c -L3 d ) X -(G5 e -U f ) Y -G3 g wherein P comprises the second promoter nucleotide sequence, and wherein a=0 or 1; N comprises one of the MHC class I epitope-encoding nucleic acid sequences, where c=1; L5 comprises the 5' linker sequence, where b=0 or 1; L3 comprises the 3' linker sequence, where d=0 or 1; G5 comprises one of said at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 166) amino acid linker, where e=0 or 1; G3 comprises one of said at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 167) amino acid linker, where g=0 or 1; U comprises one of the at least one MHC class II antigen-encoding nucleic acid sequences, where f=1; X = 1 to 400, where for each X, the corresponding N c is an epitope-encoding nucleic acid sequence, Y=0, 1, or 2, where for each Y, the corresponding U f is the antigen-encoding nucleic acid sequence] Any of the compositions of 1010 to 1021 of the present invention, described by a formula comprising: [The present invention 1024] For each X, the corresponding N c are different MHC class I epitope-encoding nucleic acid sequences. [The present invention 1025] For each Y, the corresponding U f are different MHC class II antigen-encoding nucleic acid sequences. [The present invention 1026] a=0, b=1, d=1, e=1, g=1, h=1, X=20, Y=2, the at least one promoter nucleotide sequence is a single 26S promoter nucleotide sequence provided by the backbone; the at least one polyadenylated poly(A) sequence is a poly(A) sequence of at least 100 consecutive A nucleotides (SEQ ID NO: 168) provided by the backbone; each N encodes an MHC class I epitope 7 to 15 amino acids in length; L5 is a natural 5' linker sequence encoding the natural N-terminal amino acid sequence of the MHC I epitope, the 5' linker sequence encoding a peptide that is at least 3 amino acids in length; L3 is a natural 3' linker sequence encoding the natural terminal nucleic acid sequence of the MHC I epitope, the 3' linker sequence encoding a peptide that is at least 3 amino acids in length; U is each of the PADRE class II sequence and the tetanus toxoid MHC class II sequence; the vector backbone comprises a chimpanzee adenovirus vector, optionally a ChAdV68 vector, or an alphavirus vector, optionally a Venezuelan equine encephalitis virus vector; Each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide of 13 to 25 amino acids in length. Any of compositions 1022 to 1025 of the present invention. [The present invention 1027] Any of the preceding compositions of the present invention further comprising a nanoparticulate delivery vehicle. [The present invention 1028] 1027. The composition of claim 1027, wherein said nanoparticulate delivery vehicle is a lipid nanoparticle (LNP). [The present invention 1029] 1028. The composition of claim 1028, wherein the LNP comprises an ionizable amino lipid. [The present invention 1030] 1029. The composition of claim 1029, wherein said ionizable amino lipid comprises an MC3-like (dilinoleylmethyl-4-dimethylaminobutyrate) molecule. [The present invention 1031] 1031. The composition of any of claims 1027 to 1030, wherein the nanoparticle delivery vehicle encapsulates an antigen expression system. [The present invention 1032] The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1031, wherein the antigen cassette is incorporated between the at least one promoter nucleotide sequence and the at least one poly(A) sequence. [The present invention 1033] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1032, wherein said at least one promoter nucleotide sequence is operably linked to said antigen-encoding nucleic acid sequence. [The present invention 1034] The composition of any one of inventions 1010 to 1021, 1023 to 1025, or 1027 to 1033, wherein the one or more vectors comprise one or more positive-strand RNA vectors. [This invention 1035] 1034. The composition of claim 1034, wherein the one or more positive-strand RNA vectors comprise a 5'7-methylguanosine (m7g) cap. [The present invention 1036] The composition of any one of claims 1034 to 1035, wherein the one or more positive-strand RNA vectors are generated by in vitro transcription. [This invention 1037] The composition of any one of claims 1010 to 1021, 1023 to 1025, or 1027 to 1036, wherein the one or more vectors are autonomously replicating in mammalian cells. [The present invention 1038] Any of compositions 1010 to 1021, 1023 to 1025, or 1027 to 1037, wherein the backbone comprises at least one nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus. [This invention 1039] 1027-1037. The composition of any of claims 1010-1021, 1023-1025, or 1027-1037, wherein the backbone comprises at least one nucleotide sequence of a Venezuelan equine encephalitis virus. [The present invention 1040] The composition of claim 1038 or 1039, wherein the backbone comprises at least a sequence for nonstructural protein-mediated amplification, a 26S promoter sequence, a poly(A) sequence, a nonstructural protein 1 (nsP1) gene, a nsP2 gene, a nsP3 gene, and a nsP4 gene encoded by a nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus. [This invention 1041] The composition of claim 1038 or 1039, wherein the backbone comprises at least a sequence for nonstructural protein-mediated amplification encoded by a nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus, a 26S promoter sequence, and a poly(A) sequence. [The present invention 1042] The composition of claim 1040 or 1041, wherein the sequence for non-structural protein-mediated amplification is selected from the group consisting of an alphavirus 5'UTR, a 51 nt CSE, a 24 nt CSE, a 26S subgenomic promoter sequence, a 19 nt CSE, an alphavirus 3'UTR, or a combination thereof. [This invention 1043] 1043. The composition of any of claims 1040 to 1042, wherein said scaffold does not encode the structural virion proteins capsid E2 and E1. [This invention 1044] 1043. The composition of claim 1043, wherein the antigen cassette is inserted in place of a structural virion protein within the nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus. [This invention 1045] The composition of any one of claims 1038 to 1039, wherein said Venezuelan equine encephalitis virus comprises the sequence set forth in SEQ ID NO:3 or SEQ ID NO:5. [The present invention 1046] 1038 or 1039, wherein said Venezuelan equine encephalitis virus comprises the sequence of SEQ ID NO: 3 or SEQ ID NO: 5, further comprising a deletion between base pairs 7544 and 11175. [This invention 1047] 1046. The composition of claim 1046, wherein said backbone comprises the sequence set forth in SEQ ID NO:6 or SEQ ID NO:7. [This invention 1048] 1046 or 1047, wherein the antigen cassette is inserted at position 7544 to replace the deletion between base pairs 7544 and 11175 set forth in the sequence of SEQ ID NO: 3 or SEQ ID NO: 5. [This invention 1049] The composition of any one of claims 1044 to 1048, wherein insertion of the antigen cassette results in transcription of a polycistronic RNA comprising the nsP1 to 4 genes and the at least one antigen-encoding nucleic acid sequence, and wherein the nsP1 to 4 genes and the at least one antigen-encoding nucleic acid sequence are in separate open reading frames. [The present invention 1050] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1037, wherein the backbone comprises at least one nucleotide sequence of a chimpanzee adenoviral vector. [This invention 1051] 1050. The composition of claim 1050, wherein said chimpanzee adenoviral vector is a ChAdV68 vector. [This invention 1052] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1051, wherein said at least one promoter nucleotide sequence is a native 26S promoter nucleotide sequence encoded by said backbone. [This invention 1053] The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1051, wherein said at least one promoter nucleotide sequence is an exogenous RNA promoter. [This invention 1054] The composition of any one of inventions 1010 to 1021, 1023 to 1025, or 1027 to 1053, wherein the second promoter nucleotide sequence is a 26S promoter nucleotide sequence. [This invention 1055] Any of the compositions of inventions 1010 to 1021, 1023 to 1025, or 1027 to 1053, wherein the second promoter nucleotide sequence comprises multiple 26S promoter nucleotide sequences, each 26S promoter nucleotide sequence resulting in transcription of one or more of the separate open reading frames. [This invention 1056] 1056. The composition of any of claims 1010 to 1055, wherein said one or more vectors are each at least 300 nt in size. [This invention 1057] 1057. The composition of any of claims 1010 to 1056, wherein said one or more vectors are each at least 1 kb in size. [This invention 1058] The composition of any one of claims 1010 to 1057, wherein the one or more vectors are each 2 kb in size. [This invention 1059] 1058. The composition of any one of claims 1010 to 1058, wherein said one or more vectors are each less than 5 kb in size. [The present invention 1060] 1059. The composition of any of claims 1010 to 1059, wherein at least one of said at least one antigen-encoding nucleic acid sequence encodes a polypeptide sequence or a portion thereof that is presented by an MHC class I protein. [This invention 1061] The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1060, wherein each antigen-encoding nucleic acid sequence is directly linked to one another. [This invention 1062] Any of the compositions of claims 1010 to 1021, 1023 to 1025, or 1027 to 1061, wherein at least one of the at least one antigen-encoding nucleic acid sequence is linked to a different antigen-encoding nucleic acid sequence by a nucleic acid sequence encoding a linker. [This invention 1063] 1063. The composition of claim 1062, wherein said linker links two MHC class I epitope sequences or one MHC class I epitope sequence to one MHC class II sequence. [This invention 1064] The linker may be (1) at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive glycine residues in length (SEQ ID NO: 169); (2) at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive alanine residues in length (SEQ ID NO: 170); (3) two arginine residues (RR); (4) alanine, alanine, tyrosine (AAY); or (5) a sequence that is efficiently processed by the mammalian proteasome. and (6) one or more naturally occurring sequences flanking the antigen from the cognate source protein and having a length of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 2-20 amino acid residues. [This invention 1065] 1063. The composition of claim 1062, wherein said linker links two MHC class II sequences or one MHC class II sequence to one MHC class I epitope sequence. [The present invention 1066] 1064. The composition of claim 1064, wherein said linker comprises the sequence GPGPG (SEQ ID NO: 171). [This invention 1067] Any of the compositions of claims 1010 to 1021, 1023 to 1025, or 1027 to 1066, wherein at least one of the at least one antigen-encoding nucleic acid sequences is operably or directly linked to a separate or contiguous sequence that improves expression, stability, cellular trafficking, processing and presentation, and / or immunogenicity of the at least one antigen-encoding nucleic acid sequence. [The present invention 1068] The composition of claim 1067, wherein the separated or consecutive sequences comprise at least one of a ubiquitin sequence, a ubiquitin sequence modified to enhance proteasome targeting (e.g., a ubiquitin sequence containing a Gly→Ala substitution at position 76), an immunoglobulin signal sequence (e.g., IgK), a major histocompatibility class I sequence, a lysosomal-associated membrane protein (LAMP)-1, a human dendritic cell lysosomal-associated membrane protein, and a major histocompatibility class II sequence, and optionally, the ubiquitin sequence modified to enhance proteasome targeting is A76. [This invention 1069] 1010-1021, 1023-1025, or 1027-1068, wherein the at least one antigen-encoding nucleic acid sequence comprises at least 2-10, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleic acid sequences. [The present invention 1070] Any of compositions 1001 to 1003, 1010 to 1021, 1023 to 1025, or 1027 to 1068 of the present invention, wherein the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 15 to 20, 11 to 100, 11 to 200, 11 to 300, 11 to 400, or up to 400 nucleic acid sequences. [This invention 1071] 1001-1003, 1010-1021, 1023-1025, or 1027-1068, wherein the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 2-400 nucleic acid sequences, and at least two of the antigen-encoding nucleic acid sequences encode a polypeptide sequence or a portion thereof that is presented by an MHC class I protein. [This invention 1072] 1027. The composition of claim 1022 or 1026, wherein at least two of said antigen-encoding nucleic acid sequences encode a polypeptide sequence or a portion thereof that is presented by an MHC class I protein. [This invention 1073] Any of the preceding compositions of the present invention, which, when administered to the subject and translated, causes at least one of the antigens encoded by the at least one HIV MHC class I antigen-encoding nucleic acid or said at least one of the MHC class I epitopes to be presented on antigen-presenting cells, resulting in an immune response. [This invention 1074] Any of the compositions of inventions 1001 to 1003 or 1010 to 1073, wherein when the at least one HIV MHC class I antigen-encoding nucleic acid sequence is administered to the subject and translated, at least one of the antigens is presented on antigen-presenting cells to result in an immune response, and optionally, expression of each of the at least one antigen-encoding nucleic acid sequence is driven by the at least one promoter nucleotide sequence. [This invention 1075] Any of compositions 1001-1003 or 1010-1074 of the invention, wherein each MHC class I antigen-encoding nucleic acid sequence encodes a polypeptide sequence that is 8 to 35 amino acids in length, optionally 9 to 17, 9 to 25, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 amino acids in length. [This invention 1076] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1075, wherein said at least one MHC class II antigen-encoding nucleic acid sequence is present. [This invention 1077] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1076, wherein said at least one MHC class II antigen-encoding nucleic acid sequence is 12 to 20, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 20 to 40 amino acids in length. [This invention 1078] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1077, wherein the at least one MHC class II antigen-encoding nucleic acid sequence is present and comprises at least one universal MHC class II antigen-encoding nucleic acid sequence, and optionally the at least one universal sequence comprises at least one of tetanus toxoid and PADRE. [This invention 1079] 1027-1078. The composition of any of claims 1010-1021, 1023-1025, or 1027-1078, wherein said at least one promoter nucleotide sequence or said second promoter nucleotide sequence is inducible. [The present invention 1080] 1027-1078. The composition of any of claims 1010-1021, 1023-1025, or 1027-1078, wherein said at least one promoter nucleotide sequence or said second promoter nucleotide sequence is non-inducible. [This invention 1081] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1080, wherein said at least one poly(A) sequence comprises a poly(A) sequence that is native to said backbone. [This invention 1082] 10. The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1080, wherein said at least one poly(A) sequence comprises a poly(A) sequence that is exogenous to said backbone. [This invention 1083] The composition of any of claims 1010 to 1021, 1023 to 1025, or 1027 to 1082, wherein said at least one poly(A) sequence is operably linked to at least one of said at least one antigen-encoding nucleic acid sequence. [This invention 1084] Any of compositions 1010 to 1021, 1023 to 1025, or 1027 to 1083, wherein the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides (SEQ ID NO: 172). [This invention 1085] Any of the compositions of inventions 1010 to 1021, 1023 to 1025, or 1027 to 1083, wherein said at least one poly(A) sequence is at least 100 consecutive A nucleotides (SEQ ID NO: 173). [The present invention 1086] Any of compositions 1001-1003 or 1010-1085, wherein the antigen expression system further comprises at least one of an intron sequence, a woodchuck hepatitis virus post-transcriptional regulator (WPRE) sequence, an internal ribosome entry sequence (IRES) sequence, a nucleotide sequence encoding a 2A self-cleaving peptide sequence, a nucleotide sequence encoding a furin cleavage site, or a sequence within the 5' or 3' non-coding region known to improve nuclear transport, stability, or translation efficiency of mRNA, operably linked to at least one of the at least one antigen-encoding nucleic acid sequence. [This invention 1087] Any of the compositions of claims 1001 to 1003 or 1010 to 1086, wherein the antigen expression system further comprises a reporter gene, including, but not limited to, green fluorescent protein (GFP), a GFP mutant, secreted alkaline phosphatase, luciferase, a luciferase mutant, or a detectable peptide or epitope. [This invention 1088] 1087. The composition of claim 1087, wherein said detectable peptide or epitope is selected from the group consisting of an HA tag, a Flag tag, a His tag, or a V5 tag. [This invention 1089] the at least one MHC class I antigen-encoding nucleic acid sequence is (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens will be presented by one or more of said MHC proteins, said set of numerical likelihoods having been determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on said set of numerical likelihoods to generate a set of selected antigens used to generate said at least one MHC class I antigen-encoding nucleic acid sequence; Any of compositions 1010 to 1021, 1023 to 1025, or 1027 to 1075 of the present invention selected by carrying out the above. [The present invention 1090] each of said MHC class I epitope-encoding nucleic acid sequences comprising: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens will be presented by one or more MHC proteins, said set of numerical likelihoods having been determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on said set of numerical likelihoods to generate a set of selected antigens used to generate said at least 20 MHC class I antigen-encoding nucleic acid sequences; The composition of the present invention 1022 or 1026, selected by performing the steps. [This invention 1091] The composition of claim 1009, 1089, or 1090, wherein the number of sets of selected antigens is 2 to 20. [This invention 1092] The presentation model: (a) the presence of a pair of a particular one of the MHC alleles and a particular amino acid at a particular position in the peptide sequence; (b) the likelihood of presentation of such peptide sequences containing said particular amino acids at said particular positions by said particular one of said MHC alleles of said pair; The composition of the present invention 1009 or 1089 to 1091 shows the dependency between. [This invention 1093] 1009 or 1089-1092, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being presented relative to antigens not selected based on the presentation model, and optionally the selected antigens have been validated as being presented by one or more specific MHC alleles. [This invention 1094] The composition of any one of claims 1009 to 1089, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being able to induce an immune response in response to the presence of HIV in the subject, relative to antigens not selected based on the presentation model. [This invention 1095] The composition of any one of claims 1009 to 1089, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being presented to naive T cells by professional antigen-presenting cells (APCs) relative to antigens not selected based on the presentation model, and optionally the APCs are dendritic cells (DCs). [This invention 1096] The composition of any one of claims 1009 to 1089, wherein selecting the set of selected antigens comprises selecting antigens that have a reduced likelihood of being inhibited by central or peripheral tolerance relative to antigens not selected based on the presentation model. [This invention 1097] The composition of any one of claims 1009 to 1089, wherein selecting the set of selected antigens comprises selecting antigens that have a reduced likelihood of inducing an autoimmune response against normal tissue in the subject relative to antigens not selected based on the presentation model. [This invention 1098] The composition of any one of claims 1009 to 1089, wherein the exome or transcriptome nucleotide sequencing data is obtained by performing next-generation sequencing (NGS) or any massively parallel processing sequencing approach. [This invention 1099] The composition of any one of claims 1001 to 1003 or 1010 to 1098, wherein the antigen cassette comprises a junction epitope sequence formed by adjacent sequences within the antigen cassette. [The present invention 1100] 1099. The composition of the present invention, wherein the or each junction epitope sequence has an affinity for MHC greater than 500 nM. [The present invention 1101] The composition of any one of claims 1099 to 1100, wherein each junction epitope sequence is non-self. [The present invention 1102] Any of the preceding compositions of the invention, wherein each of said MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele that is present in at least 5% of the population. [The present invention 1103] Any of the preceding compositions of the invention, wherein each of said MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA prevalence in the population of at least 0.01%. [The present invention 1104] Any of the preceding compositions of the invention, wherein each of said MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA abundance in the population of at least 0.1%. [This invention 1105] A pharmaceutical composition comprising any of the compositions of the preceding inventions and a pharmaceutically acceptable carrier. [The present invention 1106] The composition of the present invention 1105, further comprising an adjuvant. [This invention 1107] An isolated nucleotide sequence or set of isolated nucleotide sequences comprising an antigen cassette of any of the preceding composition inventions and one or more elements obtained from the sequence of SEQ ID NO:3 or SEQ ID NO:5, optionally wherein said one or more elements are selected from the group consisting of sequences required for nonstructural protein-mediated amplification, 26S promoter nucleotide sequences, poly(A) sequences, and nsP1-4 genes of the sequence set forth in SEQ ID NO:3 or SEQ ID NO:5, and optionally wherein said nucleotide sequences are cDNAs. [This invention 1108] The isolated nucleotide sequence of the present invention 1107, comprising the antigen cassette of any of the preceding composition inventions, wherein said sequence or set of isolated nucleotide sequences is inserted at position 7544 of the sequence set forth in SEQ ID NO:6 or SEQ ID NO:7. [This invention 1109] the nucleotide sequence of a T7 or SP6 RNA polymerase promoter located 5' of said one or more elements derived from the sequence of SEQ ID NO:3 or SEQ ID NO:5; optionally, one or more restriction sites located 3' of said poly(A) sequence; The isolated nucleotide sequence of claim 1107 or 1108, further comprising: [The present invention 1110] 1107. The isolated nucleotide sequence of the present invention, wherein the antigen cassette of any of the preceding composition inventions is inserted at position 7563 of SEQ ID NO:8 or SEQ ID NO:9. [The present invention 1111] A vector or a set of vectors comprising the nucleotide sequences of the present invention 1107 to 1110. [The present invention 1112] An isolated cell comprising a nucleotide sequence or a set of isolated nucleotide sequences of the present invention 1107 to 1111, optionally wherein the cell is a BHK-21, CHO, HEK293 or a mutant thereof, 911, HeLa, A549, LP-293, PER.C6, or AE1-2a cell. [The present invention 1113] A method for treating a subject with HIV, comprising administering to the subject a composition of any of the preceding composition inventions or a pharmaceutical composition of any of inventions 1105 to 1106. [This invention 1114] A method for inducing an immune response in a subject, comprising administering to the subject any of the compositions of the preceding composition inventions or any of the pharmaceutical compositions of inventions 1105 to 1106. [This invention 1115] Any of the methods of inventions 1113 to 1114, wherein the subject expresses at least one HLA allele that is predicted or known to present at least one of the MHC class I epitopes encoded by the one or more vectors of the antigen expression system. [The present invention 1116] 1116. The method of any of claims 1113 to 1115, wherein said composition is administered intramuscularly (IM), intradermally (ID), subcutaneously (SC), or intravenously (IV). [This invention 1117] 1116. The method of any one of claims 1113 to 1115, wherein the composition is administered intramuscularly. [This invention 1118] The method of any of claims 1113 to 1117, further comprising administering to said subject a second vaccine composition. [This invention 1119] The method of claim 1118, wherein said second vaccine composition is administered before the administration of the composition or pharmaceutical composition of any of claims 1113 to 1114. [The present invention 1120] The method of claim 1118, wherein said second vaccine composition is administered subsequent to the administration of the composition or pharmaceutical composition of any of claims 1113-1114. [This invention 1121] The method of any one of claims 1119 to 1120, wherein said second vaccine composition is the same as the composition or pharmaceutical composition of any one of claims 1113 to 1114. [This invention 1122] The method of any one of claims 1119 to 1120, wherein said second vaccine composition is different from the composition or pharmaceutical composition of any one of claims 1113 to 1114. [This invention 1123] 1123. The method of claim 1122, wherein said second vaccine composition comprises a chimpanzee adenoviral vector encoding at least one antigen-encoding nucleic acid sequence. [This invention 1124] 1123. The method of claim 1123, wherein said at least one antigen-encoding nucleic acid sequence encoded by said chimpanzee adenoviral vector is the same as at least one antigen-encoding nucleic acid sequence of any of the preceding composition inventions. [Invention 1125] A method for producing an antigen expression system according to any one of claims 1001 to 1004 and 1010 to 1106 of the present invention, comprising: (a) obtaining a linearized DNA sequence comprising the backbone and the antigen cassette; (b) in vitro transcribing the linearized DNA sequence by adding the linearized DNA sequence to an in vitro transcription reaction containing all components necessary for transcribing the linearized DNA sequence into RNA, optionally further comprising in vitro addition of the m7g cap to the resulting RNA; (c) isolating the one or more vectors from the in vitro transcription reaction; and The method comprising: [The present invention 1126] A method for producing 1125 of the present invention, wherein the linearized DNA sequence is generated by linearizing a DNA plasmid sequence or by amplification using PCR. [This invention 1127] 1126. The method of production of claim 1126, wherein said DNA plasmid sequence is generated using one of bacterial recombination or total genome DNA synthesis or total genome DNA synthesis with amplification of DNA synthesized within a bacterial cell. [This invention 1128] The method of producing 1125 of the present invention, wherein isolating said one or more vectors from said in vitro transcription reaction involves one or more of phenol-chloroform extraction, silica column-based purification, or similar RNA purification methods. [This invention 1129] A method for producing any one of the compositions of the present inventions 1001 to 1004 or 1010 to 1106 for delivering the antigen expression system, comprising: (a) providing a nanoparticulate delivery vehicle component; (b) providing said antigen expression system; (c) providing the composition for delivering the antigen expression system to the nanoparticulate delivery vehicle and conditions sufficient for the antigen expression system to form; The method comprising: [The present invention 1130] The method for producing the present invention 1129, wherein the conditions are provided by microfluidic mixing. [This invention 1131] 1. A method for assessing a subject for HIV, comprising: a) determining or having previously determined the HIV subtype of the subject's HIV; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 325 to 22349; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1132] 1131. The method of claim 1131, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Tables 35 to 45. [This invention 1133] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype A1; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 2165; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1134] 1133. The method of claim 1133, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 35. [This invention 1135] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype A2; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 2166 to 4106; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1136] 1135. The method of claim 1135, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 36. [This invention 1137] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype B; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 4107 to 6241; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1138] 1137. The method of claim 1137, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 37. [This invention 1139] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype C; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 6242 to 8389; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1140] 1139. The method of claim 1139, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 38. [This invention 1141] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype D; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 8930 to 10626; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1142] 1141. The method of claim 1141, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 39. [This invention 1143] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F1; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 10627 to 12810; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1144] 1143. The method of claim 1143, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 40. [Invention 1145] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F2; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 12811 to 15079; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [Invention 1146] 1145. The method of claim 1145, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 41. [This invention 1147] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype G; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 15080 to 17174; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1148] 1147. The method of claim 1147, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 42. [This invention 1149] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype H; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 17175 to 19388; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1150] 1149. The method of claim 1149, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 43. [This invention 1151] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype J; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 19389 to 21003; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1152] 1151. The method of claim 1151, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 44. [This invention 1153] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype K; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence containing at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 21004 to 22349; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1154] 1153. The method of claim 1153, wherein said HLA allele expressed by said subject is selected from the group consisting of the HLA alleles of Table 45. [This invention 1155] Any of the methods of claims 1131 to 1154, wherein determining the HIV subtype of the HIV in the subject, or having it already determined, comprises obtaining a dataset indicative of the HIV subtype from a third party that processed a sample from the subject. [Invention 1156] Any of the methods of claims 1131 to 1154, wherein determining whether the subject expresses an HLA allele, or whether it has already been determined, comprises obtaining a dataset from a third party that processed a sample from the subject. [This invention 1157] Any of the methods of claims 1131 to 1154, wherein determining whether the subject expresses an HLA allele, or has already been determined, comprises obtaining a sample from the subject and assaying the sample using a method selected from the group consisting of exome sequencing, targeted exome sequencing, transcriptome sequencing, Sanger sequencing, PCR-based genotyping assays, mass spectrometry-based methods, microarrays, nanostrings, ISH, and IHC. [This invention 1158] 1157. The method of claim 1157, wherein said sample is selected from tissue, body fluid, blood, spinal fluid, or fine needle aspirate. [This invention 1159] 1158. The method of any of claims 1131 to 1158, wherein said HLA allele has an HLA frequency of at least 1%. [The present invention 1160] 1. A method for treating a subject, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 22349. [This invention 1161] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165. [This invention 1162] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106. [This invention 1163] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107 to 6241. [This invention 1164] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389. [Invention 1165] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 8930 to 10626. [Invention 1166] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 10627 to 12810. [This invention 1167] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 12811 to 15079. [Invention 1168] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 15080 to 17174. [This invention 1169] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 17175 to 19388. [This invention 1170] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 19389 to 21003. [This invention 1171] 1. A method of treating a subject with HIV, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349. [This invention 1172] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 22349. [This invention 1173] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165. [This invention 1174] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106. [This invention 1175] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107 to 6241. [Invention 1176] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389. [This invention 1177] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence selected from the group consisting of any one of the epitope sequences of SEQ ID NOs: 8930 to 10626. [This invention 1178] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 10627 to 12810. [This invention 1179] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 12811 to 15079. [This invention 1180] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of sequences set forth in SEQ ID NOs: 15080 to 17174. [This invention 1181] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 17175 to 19388. [This invention 1182] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 19389 to 21003. [This invention 1183] 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, wherein the antigen-based vaccine 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349. [This invention 1184] 1184. The method of any of claims 1160 to 1183, wherein said subject expresses at least one HLA allele predicted or known to present said at least one MHC class I epitope sequence. [This invention 1185] determining that the subject is a candidate for receiving the antigen-based vaccine prior to administering the antigen-based vaccine to the subject; and wherein said determining further comprises: 1) the subject expresses an HLA allele known or predicted to present the at least one MHC class I epitope; and 2) the subject has been exposed to or is susceptible to exposure to the HIV subtype; Any of the methods of the present inventions 1160 to 1183, comprising identifying the [Invention 1186] 1186. The method of any of claims 1184 or 1185, wherein said at least one HLA allele is selected from the group consisting of the HLA alleles of Tables 35-45. [This invention 1187] 1187. The method of any one of claims 1131 to 1186, wherein said antigen-based vaccine comprises an antigen expression system. [This invention 1188] The method of claim 1187, wherein said antigen expression system comprises any one of said antigen expression systems of any of claims 1010 to 1104. [This invention 1189] The method of any one of claims 1131 to 1188, wherein said antigen-based vaccine comprises any one of said pharmaceutical compositions of any one of claims 1105 to 1106. [This invention 1190] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165. [This invention 1191] The composition of any one of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106. [This invention 1192] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107 to 6241. [This invention 1193] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389. [This invention 1194] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930 to 10626. [This invention 1195] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627 to 12810. [Invention 1196] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811 to 15079. [This invention 1197] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080 to 17174. [This invention 1198] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175 to 19388. [This invention 1199] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389 to 21003. [The present invention 1200] 1009. The composition of any of claims 1001 to 1009, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349. [The present invention 1201] 1. A method for assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject expresses an HLA allele; b) obtaining or having obtained sequencing data for HIV present in said subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 22349, and a second candidate epitope sequence is a variant epitope sequence, each of which is predicted to be presented by the HLA allele expressed by the subject; d) generating said antigen-based vaccine comprising said selected candidate epitope sequences; e) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1202] 1. A method for treating a subject with HIV, comprising: a) determining, or having previously determined, that the subject expresses an HLA allele; b) obtaining or having obtained sequencing data for HIV present in said subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325 to 22349, and a second candidate epitope sequence is a variant epitope sequence, each of which is predicted to be presented by the HLA allele expressed by the subject; d) generating said antigen-based vaccine comprising said selected candidate epitope sequences; e) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising: [This invention 1203] Any of the methods of claims 1001 to 1008 or 1131 to 1202, wherein the epitope sequence of any one of SEQ ID NOs: 325 to 22349 is identified by applying a presentation model trained on HLA-presented peptides sequenced by mass spectrometry. [The present invention 1204] The method of the present invention 1203, wherein the proposed model exhibits a precision value of 0.28 at a recall rate of 40%. [This invention 1205] The method of the present invention 1203, wherein the proposed model exhibits an AUC of 0.24. [Brief explanation of the drawings]

[0082] These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description and accompanying drawings.

[0083] [Figure 1] We describe the development of an in vitro T cell activating compound assay. This diagram shows the assay in which delivery of a vaccine cassette into antigen-presenting cells leads to the expression, processing, and MHC-restricted presentation of distinct peptide antigens. Reporter T cells engineered to carry T cell receptors matching specific peptide-MHC combinations are activated and express luciferase.

[0084] [Figure 2] Figure 2A illustrates the evaluation of linker sequences within the short cassette, showing two universal class II MHC epitopes (MHC-II) joined to five class I MHC class-restricted epitopes (epitopes 1-5) linked at the same positions relative to each other. Various repeats were generated using different linkers. In some cases, the T cell epitopes are directly linked to each other. In other cases, the T cell epitopes are flanked on one or both sides by their native sequence. In other repeats, the T cell epitopes are linked by the non-native sequences AAY, RR, and DPP. Figure 2B illustrates the evaluation of linker sequences within the short cassette, showing sequence information for the T cell epitopes embedded within the short cassette. The figure discloses SEQ ID NOs: 274-280, respectively, in the order shown.

[0085] [Figure 3] This paper describes the evaluation of cell targeting sequences added to a model vaccine cassette. The targeting cassette consists of a short cassette design extended with ubiquitin (Ub), signal peptide (SP), and transmembrane (TM) domains, and contains five marker human T cell epitopes (epitopes 1-5) flanked by two mouse T cell epitopes, SIINFEKL (SEQ ID NO: 80) (SII) and SPSYAYHQF (SEQ ID NO: 81) (A5), with either the non-natural linker AAY or natural linker sequences flanking the T cell epitopes (25-mer).

[0086] [Figure 4A]We describe an in vivo evaluation of the impact of epitope position within long 21mer cassettes, showing that the long cassette designs contain five marker class I epitopes (epitopes 1-5) contained within their 25mer native sequences (linker = native flanking sequences) separated by additional well-known T cell class I epitopes (epitopes 6-21) contained within their 25mer native sequences, and two universal class II epitopes (MHC-II0), differing only in the relative position of each class I epitope.

[0087] [Figure 4B]

[0023] Figure 1 illustrates the in vivo evaluation of the effect of epitope position within a long 21mer cassette and shows the sequence information of the T cell epitopes used. The figure discloses SEQ ID NOS: 281 to 301, respectively, in the order shown.

[0088] [Figure 5A] The final cassette design for preclinical IND application experiments is described, showing that the final cassette design contains 20 MHC I epitopes within their 25-mer native sequence (linker = native flanking sequence), consisting of 6 non-human primate (NHP) epitopes, 5 human epitopes, 9 mouse epitopes, and 2 universal MHC class II epitopes.

[0089] [Figure 5B] The final cassette design for preclinical IND application experiments is described, showing sequence information for the T cell epitopes used, presented on class I MHC from non-human primates, mice, and humans, as well as the sequences of two universal MHC class II epitopes, PADRE and tetanus toxoid. The figure discloses SEQ ID NOS: 302-323, respectively, in the order shown.

[0090] [Figure 6]Figure 6A illustrates the generation of ChAdV68.4WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.4WTnt.GFP DNA using the calcium phosphate protocol. Viral replication was observed 10 days after transfection, and ChAdV68.4WTnt.GFP viral plaques were visualized using a light microscope (40x magnification). Figure 6B illustrates the generation of ChAdV68.4WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.4WTnt.GFP DNA using the calcium phosphate protocol. Viral replication was observed 10 days after transfection, and ChAdV68.4WTnt.GFP viral plaques were visualized using a fluorescent microscope (40x magnification). Figure 6C illustrates the generation of ChAdV68.4WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.4WTnt.GFP DNA using a calcium phosphate protocol. Viral replication was observed 10 days after transfection, and ChAdV68.4WTnt.GFP viral plaques were visualized using a fluorescent microscope at 100x magnification.

[0091] [Figure 7]Figure 7A illustrates the generation of ChAdV68.5WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.5WTnt.GFP DNA using the Lipofectamine protocol. Viral replication (plaques) were observed 10 days after transfection. Lysates were prepared and used to reinfect 293A cells in T25 flasks. ChAdV68.5WTnt.GFP viral plaques were visualized and photographed 3 days later using a light microscope (40x magnification). Figure 7B illustrates the generation of ChAdV68.5WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.5WTnt.GFP DNA using the Lipofectamine protocol. Viral replication (plaques) were observed 10 days after transfection. Lysates were prepared and used to reinfect 293A cells in T25 flasks. ChAdV68.5WTnt.GFP viral plaques were visualized and photographed 3 days later using a fluorescent microscope at 40x magnification. Figure 7C illustrates the generation of ChAdV68.5WTnt.GFP virus after transfection. HEK293A cells were transfected with ChAdV68.5WTnt.GFP DNA using the Lipofectamine protocol. Viral replication (plaques) was observed 10 days after transfection. Lysates were prepared and used to reinfect 293A cells in T25 flasks. ChAdV68.5WTnt.GFP viral plaques were visualized and photographed 3 days later using a fluorescent microscope at 100x magnification.

[0092] [Figure 8] A scheme for generating virus particles is described.

[0093] [Figure 9] Alphavirus-derived VEE self-replicating RNA (srRNA) vectors are described.

[0094] [Figure 10]In vivo reporter expression after inoculation of C57BL / 6J mice with VEE-luciferase srRNA is demonstrated. Representative images of luciferase signals after immunization of C57BL / 6J mice with VEE-luciferase srRNA (bilateral intramuscular injection of 10 μg / mouse in MC3) at different time points are shown.

[0095] [Figure 11A] This section describes T cell responses measured 14 days after immunization with VEE srRNA formulated in MC3 LNPs in B16-OVA tumor-bearing mice. B16-OVA tumor-bearing C57BL / 6J mice were injected with 10 μg of VEE-luciferase srRNA (control), VEE-UbAAY srRNA (Vax), VEE-luciferase srRNA and anti-CTLA-4 (aCTLA-4), or VEE-UbAAY srRNA and anti-CTLA-4 (Vax + aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 7. Each group consisted of eight mice. Mice were sacrificed 14 days after immunization, and spleens and lymph nodes were harvested. SIINFEKL (SEQ ID NO: 82)-specific T cell responses were assessed by IFN-γ ELISPOT and reported as spot-forming cells (SFC) per 10 splenocytes. Each line indicates the median value.

[0096] [Figure 11B]This section describes T cell responses measured 14 days after immunization with VEE srRNA formulated in MC3 LNPs in B16-OVA tumor-bearing mice. B16-OVA tumor-bearing C57BL / 6J mice were injected with 10 μg of VEE-luciferase srRNA (control), VEE-UbAAY srRNA (Vax), VEE-luciferase srRNA and anti-CTLA-4 (aCTLA-4), or VEE-UbAAY srRNA and anti-CTLA-4 (Vax + aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 7. Each group consisted of eight mice. Mice were sacrificed 14 days after immunization, and spleens and lymph nodes were harvested. SIINFEKL (SEQ ID NO: 83)-specific T cell responses were assessed by MHCI pentamer staining and are reported as the percentage of pentamer-positive CD8+ cells. Each line indicates the median value.

[0097] [Figure 12A] Antigen-specific T cell responses after heterologous prime / boost in B16-OVA tumor-bearing mice are described. B16-OVA tumor-bearing C57BL / 6J mice were injected with adenovirus expressing GFP (Ad5-GFP) and boosted with VEE-luciferase srRNA formulated in MC3 LNPs (control) or with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. A third group was treated with Ad5-GFP prime / VEE-luciferase srRNA boost in combination with anti-CTLA-4 (aCTLA-4), and a fourth group was treated with Ad5-UbAAY prime / VEE-UbAAY boost in combination with anti-CTLA-4 (Vax+aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 21. T cell responses were measured by IFN-γ ELISPOT. Mice were sacrificed 14 days after adenovirus immunization, and spleens and lymph nodes were harvested.

[0098] [Figure 12B]Antigen-specific T cell responses after heterologous prime / boost in B16-OVA tumor-bearing mice are described. B16-OVA tumor-bearing C57BL / 6J mice were injected with adenovirus expressing GFP (Ad5-GFP) and boosted with VEE-luciferase srRNA formulated in MC3 LNPs (control) or with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. A third group was treated with Ad5-GFP prime / VEE-luciferase srRNA boost in combination with anti-CTLA-4 (aCTLA-4), and a fourth group was treated with Ad5-UbAAY prime / VEE-UbAAY boost in combination with anti-CTLA-4 (Vax+aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 21. T cell responses were measured by IFN-γ ELISPOT. Mice were sacrificed 14 days after adenovirus immunization and 14 days after srRNA boost (28 days after prime), and spleens and lymph nodes were harvested.

[0099] [Figure 12C]Antigen-specific T cell responses after heterologous prime / boost in B16-OVA tumor-bearing mice are described. B16-OVA tumor-bearing C57BL / 6J mice were injected with adenovirus expressing GFP (Ad5-GFP) and boosted with VEE-luciferase srRNA formulated in MC3 LNPs (control) or with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. A third group was treated with Ad5-GFP prime / VEE-luciferase srRNA boost in combination with anti-CTLA-4 (aCTLA-4), and a fourth group was treated with Ad5-UbAAY prime / VEE-UbAAY boost in combination with anti-CTLA-4 (Vax+aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 21. T cell responses were measured by MHC class I pentamer staining. 14 days after adenovirus immunization, mice were sacrificed and the spleens and lymph nodes were harvested.

[0100] [Figure 12D]Antigen-specific T cell responses after heterologous prime / boost in B16-OVA tumor-bearing mice are described. B16-OVA tumor-bearing C57BL / 6J mice were injected with adenovirus expressing GFP (Ad5-GFP) and boosted with VEE-luciferase srRNA formulated in MC3 LNPs (control) or with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. A third group was treated with Ad5-GFP prime / VEE-luciferase srRNA boost in combination with anti-CTLA-4 (aCTLA-4), and a fourth group was treated with Ad5-UbAAY prime / VEE-UbAAY boost in combination with anti-CTLA-4 (Vax+aCTLA-4). Additionally, all mice were treated with anti-PD-1 mAb starting on day 21. T cell responses were measured by MHC class I pentamer staining. Mice were sacrificed 14 days after adenovirus immunization and 14 days after the srRNA boost (28 days after prime), and spleens and lymph nodes were harvested.

[0101] [Figure 13A] Antigen-specific T cell responses after heterologous prime / boost in CT26 (Balb / c) tumor-bearing mice are described. Mice were immunized with Ad5-GFP and boosted 15 days after adenoviral prime with VEE-luciferase srRNA formulated in MC3 LNP (control) or primed with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. Another group received a combination of Ad5-GFP / VEE-luciferase srRNA prime / boost and anti-anti-PD-1 (aPD1), and a fourth group received a combination of Ad5-UbAAY / VEE-UbAAY prime / boost and anti-anti-PD-1 (Vax+aPD1). T cell responses to the AH1 peptide were measured using IFN-γ ELISPOT. Twelve days after adenovirus immunization, the mice were sacrificed and the spleens and lymph nodes were collected.

[0102] [Figure 13B] Antigen-specific T cell responses after heterologous prime / boost in CT26 (Balb / c) tumor-bearing mice are described. Mice were immunized with Ad5-GFP and boosted 15 days after adenoviral prime with VEE-luciferase srRNA formulated in MC3 LNP (control) or primed with Ad5-UbAAY and boosted with VEE-UbAAY srRNA (Vax). Both the control and Vax groups were also treated with an IgG control mAb. Another group received a combination of Ad5-GFP / VEE-luciferase srRNA prime / boost and anti-anti-PD-1 (aPD1), and a fourth group received a combination of Ad5-UbAAY / VEE-UbAAY prime / boost and anti-anti-PD-1 (Vax+aPD1). T cell responses to the AH1 peptide were measured using IFN-γ ELISPOT. Twelve days after adenovirus immunization and six days after srRNA boost (21 days after prime), mice were sacrificed and spleens and lymph nodes were harvested.

[0103] [Figure 14]

[0033] Figure 1 illustrates ChAdV68-induced T cell responses to murine tumor antigens in mice. Mice were immunized with ChAdV68.5WTnt.MAG2 pentamer, and T cell responses to the MHC class I epitope SIINFEKL (SEQ ID NO: 84) (OVA) were measured in C57BL / 6J female mice, and the MHC class I epitope AH1-A5 was measured in Balb / c mice. Average spot-forming cells (SFC) per 10 splenocytes measured by ELISpot assay are shown. Error bars indicate standard deviation.

[0104] [Figure 15A]Antigen-specific cellular immune responses measured by ELISpot. Antigen-specific IFN-γ production against six different mamuA01-restricted epitopes was measured in PBMCs (six rhesus macaques per group) 1, 2, 3, 4, 5, 6, 8, 9, or 10 weeks after the first boost immunization using ELISpot for the homologous prime / boost groups with VEE-MAG 25mer srRNA-LNP1 (30 μg) (FIG. 15A), VEE-MAG 25mer srRNA-LNP1 (100 μg) (FIG. 15B), or VEE-MAG 25mer srRNA-LNP2 (100 μg) (FIG. 15C), or the heterologous prime / boost group with ChAdV68.5WTnt.MAG 25mer / VEE-MAG 25mer srRNA (FIG. 15D). Results are shown in stacked bar graph format as the mean spot-forming cells (SFC) per 10 PBMC for each epitope. Values ​​for each animal were normalized to prebleed (week 0) levels.

[0105] [Figure 15B] See the legend to Figure 15A.

[0106] [Figure 15C] See the legend to Figure 15A.

[0107] [Figure 15D] See the legend to Figure 15A.

[0108] [Figure 16]Antigen-specific cellular immune responses measured using ELISpot are shown. Antigen-specific IFN-γ production against six different mamuA01-restricted epitopes was measured in PBMCs after immunization with a heterologous prime / boost regimen of ChAdV68.5WTnt.MAG25mer / VEE-MAG25mer srRNA using ELISpot before immunization and 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 weeks after the initial immunization. Results are shown in stacked bar graph format as the mean spot-forming cells (SFC) per 10 PBMCs for each epitope (six rhesus macaques per group).

[0109] [Figure 17] Figure 1 shows antigen-specific cellular immune responses measured using ELISpot. Antigen-specific IFN-γ production against six different mamuA01-restricted epitopes was measured in PBMCs after immunization with the allogeneic prime / boost regimen of VEE-MAG25mer srRNA LNP2 by ELISpot before immunization and at 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, or 15 weeks after the initial immunization. Results are shown in stacked bar graph format as the mean spot-forming cells (SFC) per 10 PBMCs for each epitope (six rhesus macaques per group).

[0110] [Figure 18] Figure 1 shows antigen-specific cellular immune responses measured using ELISpot. Antigen-specific IFN-γ production against six different mamuA01-restricted epitopes was measured in PBMCs after immunization with the allogeneic prime / boost regimen of VEE-MAG25mer srRNA LNP1 using ELISpot before immunization and 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, or 15 weeks after the initial immunization. Results are shown in stacked bar graph format as the mean spot-forming cells (SFC) per 10 PBMCs for each epitope (six rhesus macaques per group).

[0111] [Figure 19A] 1 shows an exemplary peptide spectrum generated from a dynamic range standard from Promega. The figure discloses SEQ ID NO: 324.

[0112] [Figure 19B] 1 shows an exemplary peptide spectrum generated from a dynamic range standard from Promega. The figure discloses SEQ ID NO: 324.

[0113] [Figure 20] A general TCR sequencing methodology and workflow is shown.

[0114] [Figure 21] The general organization of model epitopes from different tumors in large antigen cassettes with 30 (L), 40 (XL) or 50 (XXL) epitopes is shown.

[0115] [Figure 22] The ChAd vector expresses a long cassette, as shown by the Western blot analysis using an anti-class II (PADRE) antibody that recognizes a sequence common to all cassettes. HEK cells were infected with chAd68 vectors expressing different sized large cassettes (chAd68-50XXL, chAd68-40XL, and chAd68-30L). Infection was performed at an MOI of 0.2. 24 h postinfection, the proteasome inhibitor MG132 was added to one set of infected wells (indicated by a + sign). Another set of virus-treated wells was not treated with MG132 (indicated by a - sign). Uninfected HEK293 cells (293F) served as a negative control. 48 h postinfection, cell pellets were collected, analyzed by SDS / PAGE electrophoresis, and immunoblotted using a rabbit anti-class II PADRE antibody. HRP anti-rabbit antibody and ECL chemiluminescent substrate were used for detection.

[0116] [Figure 23]Figure 1 shows the CD8+ immune response in mice immunized with the large cassette of chAd68 detected by ICS against AH1 (top panel) and SIINFEKL (SEQ ID NO: 85) (bottom panel). Data are presented as IFNg+ cells against model epitopes as a % of total CD8 cells.

[0117] [Figure 24] Figure 1 shows CD8 responses to LD-AH1+ (top panel) and Kb-SIINFEKL (SEQ ID NO: 86)+ (bottom panel) tetramers after vaccination with the chAd68 large cassette. Data are presented as % of total CD8 cells with reactivity to the model tetramer-peptide complex. *p<0.05, **p<0.01 by ANOVA with Tukey's test. All p values ​​were compared to the MAG20 antigen cassette.

[0118] [Figure 25] Figure 1 shows CD8+ immune responses in mice treated with alphavirus large cassettes detected by ICS against AH1 (top panel) and SIINFEKL (SEQ ID NO: 87) (bottom panel). Data are presented as IFNg+ cells against model epitopes as a % of total CD8 cells. *p<0.05, **p<0.01, ***p<0.001 by ANOVA with Tukey's test. All p values ​​were compared to the MAG20 antigen cassette.

[0119] [Figure 26] Figure 1 shows the vaccination strategy for assessing the immunogenicity of antigen cassette-containing vectors in rhesus macaques. Triangles indicate vaccination with chAd68 (1e12 vp / animal) at weeks 0 and 32. Circles represent alphavirus vaccination at weeks 0, 4, 12, 12, 20, 28, and 32. Squares represent administration of anti-CTLA-4 antibody.

[0120] [Figure 27] 1 shows the time course of CD8+ anti-epitope responses in rhesus monkeys administered with chAd-MAG alone (Group 4). The mean SFC / 1e6 splenocytes is shown.

[0121] [Figure 28] 1 shows the time course of CD8+ anti-epitope responses in rhesus macaques (Group 5) administered chAd-MAG and an anti-CTLA4 antibody (ipilimumab) by IV administration. The mean SFC / 1e6 splenocytes is shown.

[0122] [Figure 29] 1 shows the time course of CD8+ anti-epitope responses in rhesus macaques (Group 6) administered with chAd-MAG and an anti-CTLA4 antibody (ipilimumab) by SC administration. The mean SFC / 1e6 splenocytes is shown.

[0123] [Figure 30] Figure 1 shows antigen-specific memory responses generated by the chAdV68 / samRNA vaccine protocol as measured by ELISpot. Results are shown as individual dot plots, with each dot representing one animal. Pre-immunization baseline (left panel) and memory responses 18 months post-prime (right panel) are shown.

[0124] [Figure 31] FIG. 1 shows memory cell phenotyping of antigen-specific CD8+ T cells by flow cytometry using combinatorial tetramer staining and CD45RA / CCR7 co-staining.

[0125] [Figure 32] The distribution of memory cell types among the four total Mamu-A*01 tetramer CD8 T cell populations at month 18 of the study is shown. Memory cells were characterized as follows: CD45RA CCR7 = naive, CD45RA CCR7 = effector (Teff), CD45RA CCR7 = central memory (Tcm), and CD45RA CCR7 = effector memory (Tem).

[0126] [Figure 33]The frequency of CD8+ T cells recognizing the CT26 tumor antigen AH1 in CT26 tumor-bearing mice is shown. P values ​​were determined using one-way ANOVA with Tukey's multiple comparison test (**P<0.001, *P<0.05). ChAdV = ChAdV68.5WTnt.MAG25mer; aCTLA4 = anti-CTLA4 antibody, clone 9D9.

[0127] [Figure 34] 1 illustrates a flow process for administering an antigen-based vaccine to a subject, according to one embodiment.

[0128] [Figure 35] 1 shows a flow process for administering an antigen-based vaccine to a subject according to a second embodiment.

[0129] [Figure 36] 1 shows the predictive performance of the EDGE model compared to published prediction tools for predicting HIV epitopes presented by class I HLA alleles. DETAILED DESCRIPTION OF THE INVENTION

[0130] Detailed Description I. Definition In general, terms used in the claims and the specification shall be interpreted as having their ordinary meaning as understood by one of ordinary skill in the art. Certain terms are defined below to provide further clarity. If there is a conflict between the ordinary meaning and a given definition, the given definition shall control.

[0131] As used herein, the term "antigen" refers to a substance that induces an immune response.

[0132] As used herein, the term "antigen-based vaccine" refers to a vaccine composition based on one or more antigens, e.g., multiple antigens. The vaccine may be nucleotide-based (e.g., virus-based, RNA-based, or DNA-based), protein-based (e.g., peptide-based), or a combination thereof.

[0133] As used herein, the term "candidate antigen" refers to an antigen that is selected for inclusion in an antigen-based vaccine.

[0134] As used herein, the term "candidate epitope sequence" refers to an epitope sequence on a candidate antigen that is selected for inclusion in an antigen-based vaccine.

[0135] As used herein, the term "coding region" refers to the portion or portions of a gene that encode a protein.

[0136] As used herein, the term "percent identity" in the context of two or more nucleic acid or polypeptide sequences refers to two or more sequences or subsequences in which a certain percentage of nucleotides or amino acid residues are the same when compared and aligned for maximum correspondence, as determined using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN, or other algorithms available to those of skill in the art), or by visual inspection. Depending on the application, the "percent identity" can exist over a region of the sequences being compared, e.g., over a functional domain, or over the full length of the two sequences being compared.

[0137] In sequence comparison, generally, one sequence serves as a reference sequence to which test sequences are compared.When using a sequence comparison algorithm, test sequences and reference sequences are input into a computer, subsequence coordinates are designated if necessary, and sequence algorithm program parameters are designated.The sequence comparison algorithm then calculates the percent sequence identity (%) of the test sequence to the reference sequence based on the designated program parameters.Alternatively, sequence similarity or difference can also be established by the combination of the presence or absence of a specific nucleotide at a selected sequence position (e.g., sequence motif) or an amino acid in a translated sequence.

[0138] Optimal alignment of sequences for comparison can be performed, for example, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra).

[0139] One example of an algorithm that is suitable for determining percent sequence identity and percent sequence similarity is the BLAST algorithm described in Altschul et al., J. Mol. Biol. 215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.

[0140] As used herein, the term "epitope" refers to a specific portion of an antigen that is typically bound by an antibody or T-cell receptor.

[0141] As used herein, the term "immunogenic" refers to the ability to elicit an immune response, for example, via T cells, B cells, or both.

[0142] As used herein, the terms "HLA binding affinity" and "MHC binding affinity" refer to the affinity of binding between a specific antigen and a specific HLA or MHC allele.

[0143] As used herein, the term "mutation" is a difference between the nucleic acid of a subject and a reference human genome used as a control.

[0144] As used herein, the term "variant calling" is the algorithmic determination, typically from sequencing, of the presence of a mutation.

[0145] As used herein, the term "polymorphism" refers to a germline mutation, ie, a mutation found in all DNA-bearing cells of an individual.

[0146] As used herein, the term "somatic mutation" is a mutation that occurs in a non-germline cell of an individual.

[0147] As used herein, the term "allele" refers to one version of a gene or one version of a gene sequence or one version of a protein.

[0148] As used herein, the term "HLA type" refers to the complement of HLA gene alleles.

[0149] As used herein, the term "exome" refers to the subset of the genome that encodes proteins. The exome can be the collection of exons of the genome.

[0150] As used herein, the term "logistic regression" is a regression model for binary data from statistics in which the logit of the probability that the dependent variable is equal to 1 is modeled as a linear function of the dependent variable.

[0151] As used herein, the term "neural network" refers to a machine learning model for classification or regression that consists of multiple layers of linear transformations followed by element-wise nonlinear transformations typically trained by stochastic gradient descent and backpropagation.

[0152] As used herein, the term "proteome" refers to the set of all proteins expressed and / or translated by a cell, a group of cells, or an individual.

[0153] As used herein, the term "peptidome" refers to the set of all peptides presented by MHC-I or MHC-II on the cell surface. Peptidome may also refer to the properties of a cell or a collection of cells.

[0154] As used herein, the term "ELISPOT" refers to enzyme-linked immunosorbent spot assay, a common method for monitoring immune responses in humans and animals.

[0155] As used herein, the term "dextramer" refers to a dextran-based peptide-MHC multimer used for antigen-specific T cell staining in flow cytometry.

[0156] As used herein, the term "tolerance or immune tolerance" refers to a state of immune unresponsiveness to one or more antigens, eg, self-antigens.

[0157] As used herein, the term "central tolerance" is tolerance conferred in the thymus by either deleting autoreactive T cell clones or promoting their differentiation into immunosuppressive regulatory T cells (Tregs).

[0158] As used herein, the term "peripheral tolerance" refers to tolerance conferred in the peripheral system by downregulating or anergizing autoreactive T cells that survive central tolerance or by promoting the differentiation of these T cells into Tregs.

[0159] The term "sample" can include a single cell, or multiple cells, or fragments of cells, or an aliquot of bodily fluid obtained from a subject by means including venipuncture, excretion, ejaculation, massage, biopsy, needle aspiration, lavage sample, scraping, surgical incision, or intervention, or other means known in the art.

[0160] The term "subject" includes cells, tissues, or organisms, human or non-human, whether male or female, in vivo, ex vivo, or in vitro. The term subject includes mammals, including humans.

[0161] The term "mammal" encompasses both humans and non-humans, and includes, but is not limited to, humans, non-human primates, canines, felines, murines, bovines, equines, and porcines.

[0162] The term "clinical factor" refers to a measurement of a subject's condition, e.g., disease activity or severity. "Clinical factor" encompasses all markers of a subject's health status, including non-sample markers, and / or other characteristics of the subject, such as, but not limited to, age and sex. A clinical factor can be a score, value, or set of values ​​that can be obtained from assessing a subject or a sample (or a population of samples) from a subject under a given condition. A clinical factor can also be predicted by other parameters, such as markers and / or gene expression surrogates. Clinical factors can include past indications (e.g., patient history) and smoking history.

[0163] The term "alphavirus" refers to members of the Togaviridae family, which are single-stranded, positive-sense RNA viruses. Alphaviruses are generally classified as Old World types, such as Sindbis, Ross River, Mayaro, Chikungunya, and Semliki Forest viruses, or New World types, such as Eastern equine encephalitis virus, Aura, Fort Morgan, or Venezuelan equine encephalitis virus and its derivative strain TC-83. Alphaviruses are generally self-replicating RNA viruses.

[0164] The term "alphavirus backbone" refers to the minimal sequence(s) of an alphavirus that allows for autonomous replication of the viral genome. The minimal sequences can include conserved sequences for nonstructural protein-mediated amplification, the nonstructural protein 1 (nsP1), nsP2, nsP3, nsP4 genes, and polyA sequences, as well as sequences for expression of subgenomic viral RNA, including the 26S promoter element.

[0165] The term "conserved sequence for nonstructural protein-mediated amplification" includes alphavirus conserved sequence elements (CSEs) well known in the art, including, but not limited to, the alphavirus 5' UTR, a 51-nt CSE, a 24-nt CSE, or other 26S subgenomic promoter sequence, a 19-nt CSE, and the alphavirus 3' UTR.

[0166] The term "RNA polymerase" includes polymerases that catalyze the production of an RNA polynucleotide from a DNA template, including, but not limited to, bacteriophage-derived polymerases, including T3, T7, and SP6.

[0167] The term "lipid" includes hydrophobic and / or amphipathic molecules. Lipids may be cationic, anionic, or neutral. Lipids may be synthetic or naturally derived and, in certain instances, biodegradable. Lipids may include cholesterol, phospholipids, lipid conjugates, including but not limited to polyethylene glycol (PEG) conjugates (PEGylated lipids), waxes, oils, glycerides, fats, and fat-soluble vitamins. Lipids may also include dilinoleylmethyl-4-dimethylaminobutyrate (MC3) and MC3-like molecules.

[0168] The term "lipid nanoparticle" or "LNP" includes vesicle-like structures, also called liposomes, formed with a lipid-containing membrane surrounding an aqueous interior. Lipid nanoparticles include lipid-based compositions with a solid lipid core stabilized by surfactants. The core lipid can be fatty acids, acylglycerols, waxes, and mixtures of these surfactants. Biological membrane lipids, such as phospholipids, sphingomyelin, bile acids (taurocholate), and sterols (cholesterol), can be used as stabilizers. Lipid nanoparticles can be formed using defined ratios of different lipid molecules, including, but not limited to, defined ratios of one or more cationic, anionic, or neutral lipids. Lipid nanoparticles can encapsulate molecules within their outer membrane shell and then be contacted with target cells to deliver the encapsulated molecules to the host cell cytosol. Lipid nanoparticles can be modified or functionalized with non-lipid molecules, such as their surface. Lipid nanoparticles can be monolamellar (unilamellar) or multilamellar (multilamellar). Lipid nanoparticles can be complexed with nucleic acids. Unilamellar lipid nanoparticles can be complexed with nucleic acids, where the nucleic acid is in the aqueous interior. Multilamellar lipid nanoparticles can be complexed with nucleic acids, where the nucleic acid is in the aqueous interior, or forming or sandwiched between them.

[0169] Abbreviations: MHC: major histocompatibility complex; HLA: human leukocyte antigen, or human MHC locus; NGS: next-generation sequencing; PPV: positive predictive value; FFPE: formalin-fixed paraffin-embedded; NMD: nonsense-mediated decay; DC: dendritic cell.

[0170] Please note that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0171] Unless otherwise specified or clear from the context, the term "about" used herein is understood to be within the range of normal tolerance in the art, for example, within two standard deviations from the mean. "About" can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from the context, all numerical values ​​set forth herein are modified by the word "about."

[0172] Terms not directly defined herein should be understood to have the meanings generally associated with them as understood within the technical field of the present invention. Certain terms are discussed herein to provide further guidance to the practitioner in describing the compositions, devices, methods, etc. of embodiments of the present invention, as well as how to make or use them. It will be recognized that multiple ways of saying the same thing may be used. Accordingly, alternative terms and synonyms may be used for any one or more of the terms discussed herein. No weight should be placed on whether a term is detailed or discussed herein. Several synonyms or alternative methods, materials, etc. are provided. The recitation of one or more synonyms or equivalents does not exclude the use of other synonyms or equivalents, unless expressly stated. The use of examples, including examples of terms, is for illustrative purposes only and does not limit the scope and meaning of the inventive embodiments herein.

[0173] All references, issued patents, and patent applications cited within the body of this specification are hereby incorporated by reference in their entirety for all purposes.

[0174] II. Methods for Identifying Antigens Methods disclosed herein describe identifying candidate antigens for inclusion in personalized antigen-based vaccines, where the candidate antigens represent antigens of infectious diseases such as HIV that are likely to be presented on the cell surface of immune cells, including professional antigen-presenting cells such as dendritic cells, and / or are likely to be immunogenic in a particular subject.

[0175] By way of example, one such method includes obtaining HIV sequencing data, wherein the HIV nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; inputting the peptide sequence of each antigen into one or more presentation models to generate a set of numerical likelihoods that each of the antigens will be presented by one or more MHC proteins of interest, wherein the set of numerical likelihoods has been identified based at least on the received mass spectrometry data; and selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens. In one embodiment, each antigen in the set of antigens is encoded by a coding region within a gene (e.g., env, gag, negative factor (nef), pol, rev, transcriptional transactivator (Tat), viral infectivity factor (vif), viral protein r (vir), or viral protein u (viu)) within the HIV genome.

[0176] The presented model comprises a statistical regression model or machine learning (e.g., deep learning) model that is trained with a set of reference data (also referred to as training data set) that includes a set of corresponding labels, and the set of reference data is optionally obtained from each of a plurality of individual subjects, some of which are infected with HIV. The reference data can further comprise mass spectrometry data, sequencing data, RNA sequencing data, expression profiling data, and proteomics data of synthetic proteins, normal human cell lines, and single-allelic cell lines that are engineered to express predetermined MHC alleles and are subsequently exposed to fresh and frozen primary samples, as well as T cell assays (e.g., ELISPOT). In certain embodiments, the set of reference data comprises each form of reference data.

[0177] The proposed model can include a set of features derived at least in part from a set of reference data, the set of features including at least one of an allele-dependent feature and an allele-independent feature. In certain embodiments, each feature is included.

[0178] The method for identifying candidate antigens also includes generating an output for constructing a personalized antigen-based vaccine by identifying one or more antigens of HIV that are likely to be presented. For example, one such method may include the steps of: acquiring HIV sequencing data, where the HIV sequencing data is used to obtain data representing each peptide sequence of a set of antigens; encoding each peptide sequence of the antigens into a corresponding numerical vector, where each numerical vector includes information about a set of amino acids that make up the peptide sequence and the position of the amino acids within the peptide sequence; inputting the numerical vectors into a deep learning presentation model using a computer processor to generate a set of presentation likelihoods for the set of antigens, where each presentation likelihood in the set represents the likelihood that the corresponding antigen will be presented by an MHC protein of a class I MHC allele; selecting a subset of the set of antigens based on the set of presentation likelihoods to generate a set of selected antigens; and generating an output for constructing a personalized antigen-based vaccine based on the set of selected antigens. In one embodiment, each antigen in the set of antigens is encoded by a gene in the genome of HIV (e.g., env, gag, nef, pol, rev, tat, vif, vir, or viu).

[0179] Specific methods for identifying antigens are well known to those of skill in the art and are described in more detail, for example, in International Patent Application Publication Nos. WO / 2017 / 106638, WO / 2018 / 195357, and WO / 2018 / 208856, each of which is incorporated by reference herein in its entirety for all purposes.

[0180] Disclosed herein is a method of treating a subject, optionally having HIV, comprising performing the steps of any of the antigen identification methods described herein, and further comprising obtaining an antigen-based vaccine comprising the set of selected antigens, and administering the antigen-based vaccine to the subject.

[0181] The methods disclosed herein can also further include identifying one or more T cells that are antigen-specific for at least one of the antigens in the subset. In some embodiments, the identifying comprises co-culturing one or more T cells with one or more of the antigens in the subset under conditions that expand the one or more antigen-specific T cells. In further embodiments, the identifying comprises contacting one or more T cells with a tetramer comprising one or more of the antigens in the subset under conditions that allow binding of the T cells to the tetramer. In even further embodiments, the methods disclosed herein can also further comprise identifying one or more T cell receptors (TCRs) of the one or more identified T cells. In certain embodiments, identifying one or more T cell receptors comprises sequencing the T cell receptor sequences of the one or more identified T cells. The methods disclosed herein can further comprise genetically engineering a plurality of T cells to express at least one of the one or more identified T cell receptors, culturing the plurality of T cells under conditions that expand the plurality of T cells, and infusing the expanded T cells into a subject. In some embodiments, engineering a plurality of T cells to express at least one of the one or more identified T cell receptors comprises cloning the T cell receptor sequences of the one or more identified T cells into an expression vector and transfecting each of the plurality of T cells with the expression vector. In certain embodiments, the methods disclosed herein further comprise culturing the one or more identified T cells under conditions that expand the one or more T cells and injecting the expanded T cells into a subject.

[0182] Also disclosed herein are isolated T cells that are antigen-specific for at least one selected antigen within said subset.

[0183] Also disclosed herein is a method for producing an HIV vaccine, the method comprising the steps of: obtaining HIV sequencing data, wherein the HIV nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; inputting the peptide sequence of each antigen into one or more presentation models to generate a set of numerical likelihoods that each of the antigens will be presented by one or more MHC alleles, the set of numerical likelihoods being identified based at least on the received mass spectrometry data; selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens; and producing an HIV vaccine comprising the set of selected antigens, or the HIV vaccine has already been produced. In one embodiment, each antigen in the set of antigens is encoded by a gene (e.g., env, gag, nef, pol, rev, tat, vif, vir, or viu) in the HIV genome.

[0184] Also disclosed herein is an antigen-based vaccine comprising a set of selected antigens selected by performing a method comprising the steps of: obtaining HIV sequencing data, where the HIV nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; inputting the peptide sequence of each antigen into one or more presentation models to generate a set of numerical likelihoods that each of the antigens will be presented by one or more MHC alleles, where the set of numerical likelihoods are identified based at least on the received mass spectrometry data; selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens; and producing an HIV vaccine comprising the set of selected antigens, or the HIV vaccine has already been produced. In one embodiment, each antigen in the set of antigens is encoded by a gene (e.g., env, gag, nef, pol, rev, tat, vif, vir, or viu) in the HIV genome.

[0185] The antigen-based vaccine may comprise one or more of a nucleotide sequence, a polypeptide sequence, RNA, DNA, a cell, a plasmid, or a vector.

[0186] An antigen-based vaccine may comprise one or more antigens that are immunogenic in a subject.

[0187] An antigen-based vaccine may not include one or more antigens that induce an autoimmune response against normal tissue in a subject.

[0188] The antigen-based vaccine may include an adjuvant.

[0189] The antigen-based vaccine may include an excipient.

[0190] The methods disclosed herein may also include selecting antigens that have an increased likelihood of being presented by the subject's immune cells relative to antigens that are not selected based on the presentation model.

[0191] The methods disclosed herein may also include selecting antigens that have an increased likelihood of being presented to naive T cells by professional antigen-presenting cells (APCs), relative to antigens not selected based on the presentation model, optionally where the APCs are dendritic cells (DCs).

[0192] The methods disclosed herein may also include selecting antigens that have an increased likelihood of being able to induce an HIV-specific immune response in a subject relative to antigens that are not selected based on the presentation model.

[0193] The methods disclosed herein may also include selecting antigens that have a reduced likelihood of being inhibited by central or peripheral tolerance relative to antigens that are not selected based on the presentation model.

[0194] The methods disclosed herein may also include selecting antigens that have a reduced likelihood of being able to induce an autoimmune response against normal tissue in a subject, relative to antigens that are not selected based on the presentation model.

[0195] Nucleotide sequencing and / or expression data of the exome or transcriptome can be obtained by sequencing tissues.

[0196] Sequencing may be next generation sequencing (NGS) or any massively parallel sequencing approach.

[0197] The set of numerical likelihoods can be further specified by at least MHC allele interaction properties, including at least one of the following: predicted affinity of binding between the MHC allele and the antigen-encoding peptide; predicted stability of the antigen-encoding peptide-MHC complex; sequence and length of the antigen-encoding peptide; probability of presentation of an antigen-encoding peptide with a similar sequence in cells from other individuals expressing the particular MHC allele, as assessed by mass spectrometry proteomics or other means; expression level of the particular MHC allele in the subject of interest (e.g., as measured by RNA-seq or mass spectrometry); probability of presentation by a particular MHC allele in other distinct individuals expressing the particular MHC allele, independent of the overall antigen-encoding peptide sequence; probability of presentation by MHC alleles of the same molecular family (e.g., HLA-A, HLA-B, HLA-C, HLA-DQ, HLA-DR, HLA-DP) in other distinct subjects, independent of the overall antigen-encoding peptide sequence.

[0198] The set of numerical likelihoods is further specified by at least MHC allele non-interacting properties, including at least one of the following: the C-terminal and N-terminal sequences flanking the antigen-encoding peptide within its source protein sequence; the presence of protease cleavage motifs within the antigen-encoding peptide, optionally weighted according to the expression of the corresponding protease in the tissue (as measured by RNA-seq or mass spectrometry); the turnover rate of the source protein measured in the appropriate cell type; the length of the source protein, the level of expression of proteasomes, immunoproteasomes, thymoproteasomes, or other proteases (which can be measured by RNA-seq, proteomic mass spectrometry, or immunohistochemistry); the expression of the source gene (e.g., env, gag, nef, pol, rev, tat, vif, vir, or viu) of the antigen-encoding peptide (e.g., RNA-seq or mass spectrometry). properties characterizing the nature of the domain of the source protein containing the peptide, for example, secondary or tertiary structure (e.g., alpha helix vs. beta sheet); alternative splicing; the probability of presentation of the peptide from the source protein of the antigen-encoding peptide in question in other individual subjects; the probability that the peptide will not be detected or will be over-represented by mass spectrometry due to technical bias; the expression / pathways of different gene modules measured by RNASeq (which does not necessarily include the source protein of the peptide), which gives information about the state of the immune cells; the probability that the peptide will bind to TAP or the measured or predicted binding affinity of the peptide to TAP; the expression level of TAP (which can be measured by RNA-seq, proteomic mass spectrometry, immunohistochemistry);These include, but are not limited to, genes encoding proteins involved in antigen presentation machinery (e.g., B2M, HLA-A, HLA-B, HLA-C, TAP-1, TAP-2, TAPBP, CALR, CNX, ERP57, HLA-DM, HLA-DMA, HLA-DMB, HLA-DO, HLA-DOA, HLA-DOB, HLA-DP, HLA-DPA1, HLA-DPB1, HLA-DQ, HLA-DQA The presence or absence of functional germline polymorphisms, including HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DR, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, or any of the genes encoding components of the proteasome or immunoproteasome; and HIV subtype (A1, A2, B, C, D, F1, F2, G, H, J, and K); smoking history.

[0199] The methods disclosed herein may also include obtaining an antigen-based vaccine comprising the selected set of antigens or a subset thereof, and optionally further comprising administering the antigen-based vaccine to a subject.

[0200] At least one of the antigens in the set of candidate antigens, when in polypeptide form, may comprise at least one of the following: a binding affinity to MHC with an IC50 value of less than 1000 nM; a length of 8-15, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids for MHC class I polypeptides; a length of 6-30, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids for MHC class II polypeptides; the presence of a sequence motif within or near the polypeptide in the parent protein sequence that promotes proteasomal cleavage; and the presence of a sequence motif that promotes TAP transport, and for MHC class II, the presence of a sequence motif within or near a peptide-facilitated cleavage site by an extracellular or lysosomal protease (e.g., cathepsin) or an HLA binding site catalyzed by HLA-DM.

[0201] The methods disclosed herein may also include selecting a subset of antigens, each of which has an increased likelihood of being presented on the surface of HIV relative to one or more other antigens.

[0202] The methods disclosed herein may also include selecting a subset of candidate antigens, and in one embodiment, the subset of candidate antigens is selected because each has an increased likelihood of being able to induce an HIV-specific immune response in a subject against one or more other antigens. In one embodiment, the subset of candidate antigens is selected because each has an increased likelihood of being able to be presented to naive T cells by professional antigen-presenting cells (APCs), optionally with respect to one or more distinct antigens, where the APCs are dendritic cells (DCs). In one embodiment, the subset of candidate antigens is selected because each has a decreased likelihood of being inhibited by central or peripheral immune tolerance against one or more other antigens. In one embodiment, the subset of antigens is selected because each has a decreased likelihood of being able to induce an autoimmune response against normal tissues in a subject against one or more other antigens.

[0203] The practice of the methods herein will employ, unless otherwise indicated, conventional methods of protein chemistry, biochemistry, recombinant DNA technology, and pharmacology, within the skill of the art. Such techniques are fully explained in the literature. See, e.g., T.E. Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman and Company, 1993); A.L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.); Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pennsylvania: Mack Publishing Company, 1990); Carey and Sundberg Advanced Organic Chemistry, 3rd Ed. (Plenum Press), Vols. A and B (1992).

[0204] III. Identification of HIV epitope sequences Also disclosed herein are methods for identifying HIV epitope sequences. In one embodiment, the HIV epitope sequences are identified from HIV nucleotide sequences sequenced from the HIV genome.

[0205] An HIV nucleotide sequence can be encoded by one of nine HIV genes, including env, gag, nef, pol, rev, tat, vif, vpr, and vpu. Sequencing of the HIV genome can be performed on a nucleic acid sample obtained from any cell type or tissue. For example, an HIV sample can be obtained from a bodily fluid, such as blood or saliva, obtained by known methods (e.g., venipuncture).

[0206] HIV nucleotide sequence information can be generated directly from millions of individual nucleic acid molecules derived from HIV. Real-time single-molecule sequencing by synthesis relies on the detection of fluorescent nucleotides as they are incorporated into nascent strands of DNA complementary to the template being sequenced. In one method, oligonucleotides 30–50 bases in length are covalently anchored at their 5′ ends to glass coverslips. These anchored strands serve two functions. First, they act as capture sites for target template strands when the template is constructed with a capture tail complementary to the surface-bound oligonucleotide. They also serve as primers for template-directed primer extension, which forms the basis for sequence reading. The capture primers serve as fixed-location sites for sequencing using multiple cycles of synthesis, detection, and chemical cleavage of the dye-linker to remove the dye. Each cycle consists of the addition of a polymerase / labeled nucleotide mixture, rinsing, imaging, and dye cleavage. In an alternative method, the polymerase is modified with a fluorescent donor molecule and immobilized on a glass slide, while each nucleotide is color-coded with an acceptor fluorescent moiety attached to the γ-phosphate. As the nucleotide becomes incorporated into the new strand, the system detects the interaction between the fluorescently tagged polymerase and the fluorescently modified nucleotide. Other sequencing-by-synthesis techniques also exist.

[0207] Any suitable sequencing-by-synthesis platform can be used to generate HIV nucleic acid sequences. As mentioned above, four major sequencing-by-synthesis platforms are currently available: the Genome Sequencer sold by Roche / 454 Life Sciences, the 1G Analyzer sold by Illumina / Solexa, the SOLiD system sold by Applied BioSystems, and the Heliscope system sold by Helicos Bioscience. Sequencing-by-synthesis platforms have also been described by Pacific BioSciences and VisiGen Biotechnologies. In some embodiments, the multiple nucleic acid molecules to be sequenced are bound to a support (e.g., a solid support). To immobilize the nucleic acids on the support, a capture sequence / universal priming site can be added to the 3' and / or 5' end of the template. The nucleic acids can be bound to the support by hybridizing the capture sequence to a complementary sequence covalently attached to the support. A capture sequence (also called a universal capture sequence) is a nucleic acid sequence complementary to a sequence attached to a support that can double as a universal primer.

[0208] As an alternative to capture sequences, a member of a coupling pair (e.g., antibody / antigen, receptor / ligand, or avidin-biotin pair, e.g., as described in U.S. Patent Application Publication No. 2006 / 0252077) can be linked to each fragment and captured on a surface coated with the respective second member of the coupling pair.

[0209] Following capture, the sequence can be analyzed by single-molecule detection / sequencing, including, for example, template-dependent sequencing by synthesis, as described, for example, in the Examples and in U.S. Patent No. 7,283,337. In sequencing by synthesis, surface-bound molecules are exposed to a multitude of labeled nucleotide triphosphates in the presence of a polymerase. The sequence of the template is determined by the order of labeled nucleotides incorporated into the 3' end of the growing strand. This can be done in real time, in a step-and-repeat mode. For real-time analysis, a different optical label can be incorporated for each nucleotide, and multiple lasers can be utilized for stimulation of the incorporated nucleotides.

[0210] Sequencing can also include other massively parallel sequencing or next-generation sequencing (NGS) techniques and platforms. Additional examples of massively parallel sequencing techniques and platforms are Illumina HiSeq or MiSeq, ThermoPGM or Proton, Pac Bio RS II or Sequel, Qiagen's Gene Reader, and Oxford Nanopore MinION. Additional similar current massively parallel sequencing technologies, and future generations of these technologies, can be used.

[0211] In some embodiments, HIV nucleotide sequences for different HIV categories, types, and subtypes are obtained from available open source databases (eg, the Los Alamos National Laboratory HIV database).

[0212] After the HIV nucleotide sequence is obtained, HIV epitope sequences are extracted from the HIV nucleotide sequence. As an example, the extraction of HIV epitope sequences can be performed by using a sliding window, where the length of the sliding window corresponds to the length of the HIV epitope sequence. To explain the extraction process, the sliding window is applied to a first HIV nucleotide sequence. A set of nucleotide base sequences within the sliding window is extracted as the first HIV epitope sequence. The sliding window is then shifted by one nucleotide base, and the next set of nucleotide base sequences within the shifted sliding window becomes the second HIV epitope sequence. This process is repeated until the sliding window has been applied to all HIV nucleotide sequences.

[0213] In one embodiment, each HIV epitope sequence is 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, or 39 nucleotide bases in length (e.g., 6-13 amino acid sequences in length). In one embodiment, each HIV epitope sequence is 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotide bases in length (e.g., 8-11 amino acid sequences in length).

[0214] Furthermore, various methods are available for detecting the presence of specific mutations in HIV sequences. Advances in this field have enabled accurate, easy, and inexpensive large-scale SNP genotyping. Several techniques have been described, including dynamic allele-specific hybridization (DASH), microplate array diagonal gel electrophoresis (MADGE), pyrosequencing, oligonucleotide-specific ligation, the TaqMan system, and various DNA "chip" technologies such as the Affymetrix SNP chip. These methods generally rely on the amplification of target gene regions by PCR. Still other methods are based on the generation of small signal molecules by invasive cleavage, followed by mass spectrometry or immobilized padlock probes and rolling circle amplification. Some of the methods known in the art for detecting specific mutations are summarized below.

[0215] PCR-based detection methods can involve simultaneous multiplex amplification of multiple markers. For example, it is well known in the art to select PCR primers to generate PCR products that do not overlap in size and can be analyzed simultaneously. Alternatively, different markers can be amplified with differentially labeled primers that can therefore be differentially detected. Of course, hybridization-based detection methods allow for differential detection of multiple PCR products in a sample. Other techniques that allow for multiplex analysis of multiple markers are also known in the art.

[0216] Several methods have been developed to facilitate the analysis of single nucleotide polymorphisms in genomic DNA or cellular RNA. For example, single nucleotide polymorphisms can be detected by using special exonuclease-resistant nucleotides, as disclosed in Mundy, CR (U.S. Pat. No. 4,656,127). According to this method, a primer complementary to the allele sequence immediately 3' from the polymorphic site is hybridized to a target molecule. If the polymorphic site on the target molecule contains a nucleotide complementary to a specific exonuclease-resistant nucleotide derivative present, the derivative is incorporated at the end of the hybridized primer. This incorporation makes the primer resistant to exonucleases, thereby enabling its detection. Since the type of exonuclease-resistant derivative in the sample is known, the fact that the primer has become resistant to exonucleases indicates that the nucleotide(s) present at the polymorphic site of the target molecule are complementary to the nucleotide(s) of the nucleotide derivative used in the reaction. This method has the advantage of not requiring the determination of a large amount of exogenous sequence data.

[0217] Solution-based methods can be used to determine the nucleotide identity at a polymorphic site (Cohen, D. et al. (French Patent No. 2,650,840; PCT Application No. WO 91 / 02087)). As in the method of Mundy, U.S. Pat. No. 4,656,127, a primer is used that is complementary to the allelic sequence immediately 3' to the polymorphic site. This method uses a labeled dideoxynucleotide derivative that is incorporated onto the end of the primer when it is complementary to the nucleotide at the polymorphic site to determine the nucleotide identity at that site.

[0218] An alternative method known as Genetic Bit Analysis (GBA) is described by Goelet, P. et al. (PCT Application No. 92 / 15712). The Goelet, P. et al. method uses a mixture of labeled terminators and primers complementary to the sequence 3' of the polymorphic site. Thus, the incorporated labeled terminators are determined by and complementary to the nucleotides present at the polymorphic site of the target molecule being evaluated. In contrast to the method of Cohen et al. (FR 2,650,840; PCT Application No. WO91 / 02087), the Goelet, P. et al. method can be a heterogeneous phase assay in which the primers or target molecules are immobilized on a solid phase.

[0219] IV. Antigen Antigens can comprise nucleotides or polypeptides. For example, antigens can be RNA sequences that encode polypeptide sequences. Thus, antigens useful in vaccines include nucleotide sequences or polypeptide sequences. In one embodiment, antigenic peptides can be described in terms of their coding sequences, and antigens comprise nucleotide sequences (e.g., DNA or RNA) that encode the relevant polypeptide sequences. In one embodiment, antigens bind to MHC proteins and are thus presented by antigen-presenting cells, allowing epitope sequences on the antigen to bind to T cell receptors. In some situations, antigens bind to MHC class I proteins. In some situations, antigens bind to MHC class II proteins. In some situations, antigens bind to both MHC class I and class II proteins.

[0220] Antigens may be from either of the two major categories of HIV (HIV-1 or HIV-2). Additionally, antigens may be from different types of HIV-1, including Group N, Group O, or Group P. Additionally, antigens from Group N may be from one of subtypes A1, A2, B, C, D, F1, F2, G, H, J, or K.

[0221] Antigens (and corresponding epitope sequences) from HIV can vary depending on the category, type, or subtype of HIV. For example, epitope sequences for HIV antigens from different HIV subtypes are shown in column 2 of Tables 35-45. Additionally, there are many epitope sequences that are invariant across HIV subtypes. Therefore, a particular epitope sequence may be included in more than one of Tables 35-45.

[0222] The one or more polypeptides encoded by the antigen nucleotide sequence can comprise at least one of the following: a binding affinity to MHC with an IC50 value of less than 1000 nM; a length of 8-15, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids for MHC class I peptides; the presence of a sequence motif within or near the peptide that promotes proteasomal cleavage and the presence of a sequence motif that promotes TAP transport; a length of 6-30, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids for MHC class II polypeptides; the presence of a sequence motif within or near the peptide-promoted cleavage site by an extracellular or lysosomal protease (e.g., cathepsin) or the HLA binding site catalyzed by HLA-DM.

[0223] The one or more antigens can be present on HIV.

[0224] The one or more antigens can be immunogenic in a subject with a tumor, e.g., can elicit a T cell or B cell response in the subject. Optionally, the subject can have HIV.

[0225] One or more antigens that induce an autoimmune response in a subject can optionally be excluded from consideration in the context of generating a vaccine for a subject with HIV.

[0226] The size of the at least one antigenic peptide molecule can be about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33, about 34, about 35, The antigenic peptide molecule can include, but is not limited to, about 36, about 37, about 38, about 39, about 40, about 41, about 42, about 43, about 44, about 45, about 46, about 47, about 48, about 49, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, or more amino acid residues, and any range derivable therein. In a specific embodiment, the antigenic peptide molecule is 50 amino acids or less.

[0227] Antigenic peptides and polypeptides can be 15 residues or less in length, typically between about 8 and about 11 residues, particularly 9 or 10 residues, for MHC class I; and 6 to 30 residues for MHC class II.

[0228] If desired, longer peptides can be designed in several ways. In one example, where the likelihood of presentation of a peptide on an HLA allele is predicted or known, the longer peptide can consist of either: (1) individual presented peptides with extensions of 2-5 amino acids toward the N- and C-termini of each corresponding gene product; or (2) a concatenation of some or all of the presented peptides, each with an extended sequence. The use of longer peptides may allow for endogenous processing by patient cells, resulting in more effective antigen presentation and induction of T cell responses.

[0229] Antigenic peptides and polypeptides can be presented on HLA proteins. In some embodiments, the antigenic peptide or polypeptide can have an IC50 of at least 5000 nM, at least 1000 nM, at least 500 nM, at least 250 nM, at least 200 nM, at least 150 nM, at least 100 nM, at least 50 nM, or less.

[0230] In some embodiments, the antigenic peptides and polypeptides do not induce an autoimmune response and / or do not cause immune tolerance when administered to a subject.

[0231] Antigenic peptides and polypeptides with desired activities or properties can be modified to confer certain desirable attributes, e.g., improved pharmacological characteristics, while at least retaining substantially all or augmenting the biological activity of the unmodified peptide, which binds to desired MHC molecules and activates appropriate T cells. For example, antigenic peptides and polypeptides can be further subjected to various modifications, such as conservative or non-conservative substitutions, which may provide certain advantages in their use, such as improved MHC binding, stability, or presentation. Conservative substitutions refer to the replacement of an amino acid residue with another that is biologically and / or chemically similar, e.g., one hydrophobic residue with another hydrophobic residue, or one polar residue with another polar residue. Substitutions include combinations such as Gly, Ala; Val, Ile, Leu, Met; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe, Tyr. The effects of single amino acid substitutions can also be explored using D-amino acids. Such modifications can be carried out using well-known peptide synthesis procedures, as described, for example, in Merrifield, Science 232:341-347 (1986), Barany & Merrifield, The Peptides, Gross & Meienhofer, eds. (NY, Academic Press), pp. 1-284 (1979); and Stewart & Young, Solid Phase Peptide Synthesis, (Rockford, Ill., Pierce), 2nd Ed. (1984).

[0232] Modification of peptides and polypeptides with various amino acid mimetics or unnatural amino acids can be particularly useful for increasing peptide and polypeptide stability in vivo. Stability can be assayed in a number of ways. For example, peptidases and various biological media, such as human plasma and serum, have been used to test stability. See, e.g., Verhoef et al., Eur. J. Drug Metab Pharmacokin. 11:291-302 (1986). Peptide half-life can be conveniently determined using a 25% human serum (v / v) assay. The protocol generally follows: Pooled human serum (type AB, non-heat-inactivated) is defatted by centrifugation before use. The serum is then diluted to 25% with RPMI tissue culture medium and used to test peptide stability. At predetermined time intervals, small aliquots of the reaction solution are removed and added to either 6% aqueous trichloroacetic acid or ethanol. The cloudy reaction sample is cooled (4°C) for 15 minutes and then spun to precipitate the precipitated serum proteins. The presence of the peptide is then determined by reverse-phase HPLC using stability-specific chromatography conditions.

[0233] Peptides and polypeptides can be modified to provide desirable attributes other than improved serum half-life. For example, the ability of a peptide to induce CTL activity can be enhanced by linking it to a sequence containing at least one epitope capable of inducing a T helper cell response. The immunogenic peptide / T helper conjugate can be linked by a spacer molecule. The spacer is typically composed of relatively small, neutral molecules, such as amino acids or amino acid mimetics, that are substantially uncharged under physiological conditions. The spacer is typically selected from, for example, Ala, Gly, or other neutral spacers of nonpolar or neutral polar amino acids. It will be understood that the optional spacer need not be composed of the same residues and can therefore be a hetero- or homo-oligomer. If present, the spacer will usually be at least one or two residues, more usually three to six residues. Alternatively, the peptide can be linked to the T helper peptide without a spacer.

[0234] The antigenic peptide can be linked to the T helper peptide at either the amino or carboxy terminus of the peptide, either directly or via a spacer. The amino terminus of either the antigenic peptide or the T helper peptide can be acylated. Exemplary T helper peptides include tetanus toxoid at 830-843, influenza at 307-319, and malaria sporozoites at around 382-398 and 378-389.

[0235] Proteins or peptides can be produced by any technique known to those of skill in the art, including expressing proteins, polypeptides, or peptides through standard molecular biology techniques, isolating proteins or peptides from natural sources, or chemically synthesizing proteins or peptides. Nucleotide and protein, polypeptide, and peptide sequences corresponding to various genes have been previously disclosed and can be found in computerized databases known to those of skill in the art. One such database is the Genbank and GenPept databases of the National Center for Biotechnology Information, located on the National Institutes of Health website. The coding regions of known genes can be amplified and / or expressed using the techniques disclosed herein or as known to those of skill in the art. Alternatively, various commercial preparations of proteins, polypeptides, and peptides are known to those of skill in the art.

[0236] In a further embodiment, the antigen comprises a nucleic acid (e.g., a polynucleotide) encoding an antigenic peptide or a portion thereof. The polynucleotide can be, for example, a single-stranded and / or double-stranded polynucleotide, such as DNA, cDNA, PNA, CNA, RNA (e.g., mRNA), or a polynucleotide having a phosphorothioate backbone, either in a natural or stabilized form, or a combination thereof, and may or may not contain introns. Yet a further embodiment provides an expression vector capable of expressing the polypeptide or a portion thereof. Expression vectors for various cell types are well known in the art and can be selected without undue experimentation. Generally, the DNA is inserted into an expression vector, such as a plasmid, in the proper orientation and correct reading frame for expression. If necessary, the DNA can be linked to appropriate transcriptional and translational regulatory control nucleotide sequences recognized by the desired host; such controls are generally available in the expression vector. The vector is then introduced into the host through standard techniques. Guidance can be found, for example, in Sambrook et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

[0237] V. Vaccine Compositions Also disclosed herein are immunogenic compositions, e.g., vaccine compositions, that are capable of generating a specific immune response, e.g., an HIV-specific immune response. Vaccine compositions typically include one or more antigens selected using the methods described herein.

[0238] In one embodiment, the vaccine composition comprises one antigen having an epitope sequence selected from any one of SEQ ID NOS: 325-22349. In other embodiments, the vaccine composition comprises multiple antigens having epitope sequences selected from any one of SEQ ID NOS: 325-22349. In such a situation, at least two of the multiple antigens may be different peptides. By different peptides, it is meant that the peptides differ in length, amino acid sequence, or both.

[0239] In some embodiments, the vaccine composition comprises one or more epitope-encoding nucleic acid sequences. In one embodiment, the epitope-encoding nucleic acid sequences are MHC class I epitope-encoding nucleic acid sequences. Each epitope-encoding nucleic acid sequence can encode an antigen having an epitope sequence selected from any one of SEQ ID NOs: 325 to 22349.

[0240] In some aspects, the vaccine composition can comprise 1 to 30 peptides, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 different peptides, 6, 7, 8, 9, 10 11, 12, 13, or 14 different peptides, or 12, 13, or 14 different peptides. In various embodiments, the peptides included in the vaccine composition comprise an epitope sequence selected from any one of SEQ ID NOs: 325-22349 set forth in Tables 35-45. The peptides may have post-translational modifications. The vaccines contain 1 to 100 or more nucleotide sequences: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 , 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more different nucleotide sequences, 6, 7, 8, 9, 10 11, 12, 13, or 14 different antigen-encoding nucleic acid sequences, or 12, 13, or 14 different antigen-encoding nucleic acid sequences.The vaccine contains 1–30 antigen sequences, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, It may comprise 5, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98, 99, 100 or more different antigen sequences, 6, 7, 8, 9, 10 11, 12, 13, or 14 different antigen sequences, or 12, 13, or 14 different antigen sequences. The vaccine contains 1–30 antigen-coding sequences: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121 The antigen coding sequence may include 5, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more different antigen coding sequences, 6, 7, 8, 9, 10 11, 12, 13, or 14 different antigen coding sequences, or 12, 13, or 14 different antigen coding sequences. In various embodiments, the antigen coding sequence encodes an antigen comprising an epitope sequence selected from any one of SEQ ID NOs: 325-22349 set forth in Tables 35-45.

[0241] Further details on the selection of candidate epitope sequences or antigen-encoding nucleic acid sequences for inclusion in vaccine compositions are provided below.

[0242] In one embodiment, the different peptides and / or polypeptides, or the nucleotide sequences encoding them, are selected such that the peptides and / or polypeptides are capable of binding to different MHC molecules, such as different MHC class I molecules and / or different MHC class II molecules. In some embodiments, a vaccine composition comprises coding sequences for peptides and / or polypeptides capable of binding to the most frequently occurring MHC class I molecules and / or different MHC class II molecules. Thus, the vaccine composition can comprise different fragments capable of binding to at least two preferred, at least three preferred, or at least four preferred MHC class I molecules and / or different MHC class II molecules.

[0243] The vaccine composition may generate a specific cytotoxic T cell response and / or a specific helper T cell response.

[0244] Antigens can also be derived from vaccinia, fowlpox, self-replicating alphaviruses, Maraba virus, adenovirus (see, e.g., Tatsis et al., Adenoviruses, Molecular Therapy (2004) 10, 616-629), or lentiviruses, including, but not limited to, second, third, or hybrid second / third generation lentiviruses, and any generation of recombinant lentiviruses designed to target specific cell types or receptors (see, e.g., Hu et al., Immunization Delivered by Lentiviral Vectors for Cancer and Infectious Diseases, Immunol Rev. (2011) 239(1):45-61; Sakuma et al., Lentiviral vectors: basic to translational, Biochem J. (2012) 443(3):603-18; Cooper et al., Rescue of splicing-mediated intron loss maximizes expression in lentiviral vectors containing the human They can also be included in viral vector-based vaccine platforms, such as the ubiquitin C promoter, Nucl. Acids Res. (2015) 43(1):682-690; Zufferey et al., Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery, J. Virol. (1998) 72(12):9873-9880. Depending on the packaging capacity of the viral vector-based vaccine platform described above, this approach can deliver one or more nucleotide sequences encoding one or more antigenic peptides.The sequence may be flanked by non-mutated sequences, separated by linkers, or preceded by one or more sequences that target intracellular compartments (see, e.g., Gros et al., Prospective identification of antigen-specific lymphocytes in the peripheral blood of melanoma patients, Nat Med. (2016) 22(4): 433-8; Stronen et al., Targeting of cancer antigens with donor-derived T cell receptor repertoires, Science. (2016) 352(6291): 1337-41; Lu et al., Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions, Clin Cancer Res. (2014) 20( 13): 3401-10). Upon introduction into the host, the infected cells express the antigen, thereby eliciting a host immune (e.g., CTL) response against the peptide. Vaccinia vectors and methods useful in immunization protocols are described, for example, in U.S. Patent No. 4,722,848. Another vector is BCG (Bacille Calmette-Guerin). BCG vectors are described by Stover et al. (Nature 351:456-460 (1991)). A wide variety of other vaccine vectors useful for therapeutic administration of antigens or immunization, such as Salmonella typhi vectors, will be apparent to those skilled in the art from the description herein.

[0245] Selection of VA antigen vaccine sequences Selected candidate antigens having epitope sequences were included in the antigen-based vaccine. In various embodiments, the epitope sequences of the candidate antigens were selected using a display model, as described in further detail below in connection with the display model. In various embodiments, the epitope sequences of the candidate antigens were selected using the Los Alamos Best-defined ("A-list") CTL epitopes, which are incorporated by reference in their entirety. 108 In various embodiments, epitope sequences for candidate antigens are selected using a display model developed to evaluate epitope sequences from the Los Alamos Best-defined ("A-list") CTL epitopes. 108 While the following description focuses on the inclusion of antigenic peptides in antigen-based vaccines, one of skill in the art will understand that the following description also applies to the inclusion of antigen-encoding nucleic acid sequences that encode these antigenic peptides in antigen cassettes. Further details of antigen cassettes are provided below.

[0246] In one aspect, each antigen-based vaccine can be developed for patients with a haplotype containing one or more specific HLA alleles. Thus, patients with a specific HLA can be treated or vaccinated with an antigen-based vaccine specifically developed for that specific HLA allele. In some aspects, each antigen-based vaccine can be developed for patients with a haplotype containing a specific combination of HLA alleles. In one embodiment, the specific HLA allele combination is known to be expressed by a population of individuals of a specific ancestral lineage. Therefore, patients of that ancestral lineage are also likely to express that HLA allele combination and therefore may be candidates for a vaccine containing antigens likely to be presented by the expressed HLA allele combination. In some aspects, an antigen-based vaccine can be developed that contains a sufficient number of antigens so that patients of any ancestral lineage are likely to present a subset of the antigens included in the antigen-based vaccine. In other words, if a sufficient number of antigens are included in the antigen-based vaccine, such an antigen-based vaccine can be effective for all patients.

[0247] Examples include the following HLA alleles: A0101, A0201, A0203, A0204, A0205, A0206, A0207, A0208, A0301, A0302, A1101, A2301, A2402, A2501, A2601, A2602, A2603, A2901, A2902, A3001, A3002, A3004, A 3101, A3201, A3301, A3303, A6801, A6802, B0702, B0801, B1301, B1302, B1401, B1402, B15 01, B1502, B1503, B1510, B1513, B1801, B2702, B2705, B3501, B3502, B3503, B3508, B3512, B3701, B3801, B3901, B3906, B4001, B4002, B4006, B4102, B4402, B4403, B4405, B4601, B4 801, B4901, B5001, B5101, B5401, B5501, B5502, B5601, B5701, B5801, C0102, C0202, C030 Antigen-based vaccines can be developed against any one or more of SEQ ID NOS: 2, C0303, C0304, C0401, C0501, C0602, C0701, C0702, C0704, C0801, C0802, C0803, C1203, C1402, C1403, C1502, C1601, C1602, C1604, and C1701. Antigens for inclusion in the antigen-based vaccine can be selected by reference to Tables 35-45 (e.g., any one of SEQ ID NOS: 325-22349), and the relevant epitope sequence for each included antigen is selected by identifying the row representing the particular HLA allele against which the antigen-based vaccine is developed. It is important to note that certain epitope sequences are consistent across multiple HIV subtypes and therefore appear across multiple tables in Tables 35-45. In some embodiments, antigens for inclusion in an antigen-based vaccine can each comprise an epitope sequence that appears in one or more of Tables 35-45. Additionally, antigens for inclusion in an antigen-based vaccine can be selected from a list of validated HIV epitopes.Examples of validated HIV epitopes can be found in the journal article "Best-Characterized HIV-1 CTL Epitopes: The 2013 Update," which is incorporated herein by reference in its entirety (the article lists the validated HIV epitopes as "best defined HIV CTL epitopes" in Table IA-1). 105 Further examples of validated HIV epitopes can be found in the journal article "The 2019 Optimal HIV CTL epitopes update: Growing diversity in epitope length and HLA restriction," which is incorporated herein by reference in its entirety. 109 .

[0248] For example, referring to row 1 of Table 35, if an antigen-based vaccine is being developed for the A2501 HLA allele, the epitope sequence "DTIAIAVAGW (SEQ ID NO: 756)" can be selected for inclusion. Such an antigen-based vaccine can include additional epitope sequences from Tables 35-45 that share a row with the A2501 HLA allele. For example, referring to Table 36, the epitope sequence "DTIAVAVAEW" (SEQ ID NO: 2606) can be further selected for inclusion in the antigen-based vaccine.

[0249] In some embodiments, antigen-based vaccines can be developed for the above-mentioned HLA allele combinations. For example, if a combination of HLA alleles is known to be expressed together by a subject, an antigen-based vaccine can be developed for that combination of expressed HLA alleles. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 HLA alleles are included in the allele combination. Antigens for inclusion in the antigen-based vaccine can be selected by referring to Tables 35-45 (e.g., any one of SEQ ID NOS: 325-22349), and the relevant epitope sequence of each included antigen can be selected by identifying the row that represents any one HLA allele in the HLA allele combination.

[0250] In one embodiment, each antigen-based vaccine can be developed for patients infected with, exposed to, or susceptible to a particular category, type, or subtype of HIV, and thus, patients can be treated or vaccinated with an antigen-based vaccine developed specifically for the category, type, or subtype of HIV to which the patient is infected, exposed, or susceptible.

[0251] For example, an antigen-based vaccine can be developed against any one of the HIV categories (e.g., HIV-1 or HIV-2), types (Group N, Group O, or Group P), or subtypes (A1, A2, B, C, D, F1, F2, G, H, J, or K). Antigens for inclusion in the antigen-based vaccine can be selected by reference to Tables 35-45 (e.g., any one of SEQ ID NOs: 325-22349).

[0252] In various embodiments, an antigen-based vaccine developed against HIV subtype A1 can include one or more antigens having the HIV epitope sequences shown in Table 35 (e.g., any one of SEQ ID NOs: 325-2165).

[0253] In various embodiments, an antigen-based vaccine developed against HIV subtype A2 can include one or more antigens having the HIV epitope sequences shown in Table 36 (e.g., any one of SEQ ID NOs: 2166-4106).

[0254] In various embodiments, an antigen-based vaccine developed against HIV subtype B can include one or more antigens having the HIV epitope sequences shown in Table 37 (e.g., any one of SEQ ID NOs: 2166-4106).

[0255] In various embodiments, an antigen-based vaccine developed against HIV subtype C can include one or more antigens having the HIV epitope sequences shown in Table 38 (e.g., any one of SEQ ID NOs: 6242-8389).

[0256] In various embodiments, an antigen-based vaccine developed against HIV subtype D can include one or more antigens having the HIV epitope sequences shown in Table 39 (e.g., any one of SEQ ID NOs: 8930-10626).

[0257] In various embodiments, an antigen-based vaccine developed against HIV subtype F1 can include one or more antigens having the HIV epitope sequences shown in Table 40 (e.g., any one of SEQ ID NOs: 10627-12810).

[0258] In various embodiments, an antigen-based vaccine developed against HIV subtype F2 can include one or more antigens having the HIV epitope sequences shown in Table 41 (e.g., any one of SEQ ID NOs: 12811-15079).

[0259] In various embodiments, an antigen-based vaccine developed against HIV subtype G can include one or more antigens having the HIV epitope sequences shown in Table 42 (e.g., any one of SEQ ID NOs: 15080-17174).

[0260] In various embodiments, an antigen-based vaccine developed against HIV subtype H can include one or more antigens having the HIV epitope sequences shown in Table 43 (e.g., any one of SEQ ID NOs: 17175-19388).

[0261] In various embodiments, an antigen-based vaccine developed against HIV subtype J can include one or more antigens having the HIV epitope sequences shown in Table 44 (e.g., any one of SEQ ID NOs: 19389-21003).

[0262] In various embodiments, an antigen-based vaccine developed against HIV subtype K can include one or more antigens having the HIV epitope sequences shown in Table 45 (e.g., any one of SEQ ID NOs: 21004-22349).

[0263] In one aspect, each antigen-based vaccine can be developed for a patient taking into account both 1) the patient's HLA type, including expression of one or more particular HLA alleles, and 2) the particular category, type, or subtype of HIV to which the patient is infected, exposed, or susceptible. By way of example, a patient who expresses particular HLA alleles and is exposed to or susceptible to a certain subtype of HIV can be treated or vaccinated with an antigen-based vaccine developed specifically for that subtype of HIV and the patient's expressed HLA type. Antigens for inclusion in the antigen-based vaccine can be selected by reference to one of Tables 35-45 (e.g., any one of SEQ ID NOS: 325-22349), and the relevant epitope sequence for each of the included antigens is selected by identifying the row in that table that lists the particular HLA allele.

[0264] For example, an antigen-based vaccine can be developed for HIV subtype A1 and for patients with the B4102 HLA allele. Referring to Table 35, a first antigen having the epitope sequence "AEVVQKVTM (SEQ ID NO: 1594)" and a second antigen having the epitope sequence "AEVVQKVVM (SEQ ID NO: 1595)" can be selected for inclusion in the antigen-based vaccine. Such an antigen-based vaccine can include additional HIV epitope sequences from Table 35 that share a row with the B4102 HLA allele (e.g., any of SEQ ID NOs: 1594-1642). As another example, an antigen-based vaccine can be developed for HIV subtype A2 and for patients with the B4001 HLA allele. Referring to Table 36, a first antigen having the epitope sequence "TESNDTITL (SEQ ID NO: 3424)" and a second antigen having the epitope sequence "AEDPEREVL (SEQ ID NO: 3425)" can be selected for inclusion in the antigen-based vaccine. Such antigen-based vaccines can include additional HIV epitope sequences from Table 36 that share a row with the B4001 HLA allele (eg, any of SEQ ID NOS: 3424-3458).

[0265] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by the HIV epitope coding sequence can include any of SEQ ID NOs: 325-328, 2166-2178, 4107-4113, 6242-6248, 8390-8397, 10627-10633, 12811-12820, 15080-15086, 17175-17184, 19389-19396, or 21004-21009.

[0266] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by the HIV epitope coding sequence can include any of SEQ ID NOs: 329-353, 2179-2200, 4114-4134, 6249-6270, 8398-8415, 10634-10654, 12821-12850, 15087-15107, 17185-17213, 19397-19420, or 21010-21031.

[0267] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 354-403, 2201-2248, 4135-4177, 6271-6315, 8416-8474, 10655-10700, 12851-12912, 15108-15155, 17214-17264, 19421-19463, or 21032-21064.

[0268] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 404-469, 2249-2326, 4178-4261, 6316-6400, 8475-8558, 10701-10768, 12913-12994, 15156-15214, 17265-17349, 19464-19518, 21065-21117.

[0269] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 470-526, 2327-2379, 6401-6450, 8559-8626, 10769-10822, 12995-13056, 15215-15263, 17350-17405, 19519-19570, and 21118-21161.

[0270] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by the HIV epitope coding sequence can include any of SEQ ID NOs: 527-565, 2380-2421, 6451-6492, 8627-8671, 10823-10867, 10357-13098, 15264-15292, 17406-17448, 19571-19604, and 21162-21192.

[0271] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by the HIV epitope coding sequence can include any of SEQ ID NOs: 566-587, 2422-2438, 6493-6509, 8672-8689, 10868-10887, 13099-13125, 15293-15307, 17449-17473, 19605-19618, and 21193-21205.

[0272] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 588-630, 2439-2477, 6510-6548, 8690-8733, 10888-10931, 13126-13179, 15308-15336, 17474-17512, 19619-19649, and 21206-21233.

[0273] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by the HIV epitope coding sequence can include any of SEQ ID NOs: 631-650, 2478-2501, 6549-6573, 8734-8761, 10932-10969, 13180-13224, 15337-15354, 17513-17543, 19650-19665, and 21234-21247.

[0274] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 651-682, 2502-2541, 6574-6618, 8762-8809, 10970-11026, 13225-13290, 15355-15396, 17544-17603, 19666-19697, and 21248-21274.

[0275] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in the antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 683-726, 2542-2583, 6619-6668, 8810-8862, 11027-11087, 13291-13370, 15397-15451, 17604-17652, 19698-19726, and 21275-21309.

[0276] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 727-741, 2584-2593, 6669-6685, 8863-8871, 11088-11103, 13371-13385, 15452-15465, 17653-17667, 19727-19738, and 21310-21317. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A2301.

[0277] In certain embodiments, one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 742-755, 2594-2605, 6686-6698, 8872-8885, 11104-11116, 13386-13397, 15466-15479, 17668-17679, 19739-19750, and 21318-21323. Such antigen-based vaccines can be useful in treating patients who express HLA allele A2402.

[0278] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 756-769, 2606-2622, 6699-6711, 8886-8903, 11117-11132, 13398-13414, 15480-15505, 17680-17693, 19751-19760, and 21324-21333. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A2501.

[0279] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 770-783, 2623-2640, 6712-6728, 8904-8927, 11133-11155, 13415-13433, 15506-15533, 17694-17714, 19761-19773, and 21334-21346. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A2601.

[0280] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 784-790, 2641-2652, 6729-6739, 8928-8937, 11156-11168, 13434-13446, 1553-15550, 17715-17723, 19774-19782, and 21347-21353. Such antigen-based vaccines can be useful in treating patients who express HLA allele A2602.

[0281] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 791-802, 2653-2671, 6740-6759, 8938-8959, 11169-11189, 13447-13464, 15551-15569, 17724-17739, 19783-19797, and 21354-21360. Such antigen-based vaccines can be useful in treating patients who express HLA allele A2603.

[0282] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 803-814, 2672-2679, 6760-6768, 8960-8976, 11190-11195, 13465-13474, 15570-15588, 17740-17751, 19798-19808, and 21361-21366. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A2901.

[0283] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 815-828, 2680-2698, 6769-6784, 8977-9000, 11196-11210, 13475-13493, 15589-15612, 17752-17773, 19809-19821, and 21367-21376. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A2902.

[0284] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 829-842, 2699-2707, 6785-6793, 9001-9012, 11211-11216, 13494-13501, 15613-15617, 17774-17781, 19822-19828, and 21377-21383. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3001.

[0285] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 843-857, 2708-2722, 6794-6807, 9013-9040, 11217-11235, 13502-13519, 15618-15636, 17782-17809, 19829-19843, and 21384-21390. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3002.

[0286] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 858-864, 2723-2728, 6808-6817, 9041-9060, 11236-11246, 13520-13530, 15637-15649, 17810-17828, 19844-19850, and 21391-21393. Such antigen-based vaccines can be useful in treating patients who express HLA allele A3004.

[0287] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 865-895, 2729-2757, 6818-6846, 9061-9082, 11247-11272, 13531-13558, 15650-15683, 17829-17862, 19851-19869, and 21394-21407. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3101.

[0288] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 896-899, 2758-2761, 6847-6850, 9083-9091, 11273-11275, 13559-13567, 15684-15688, 17863-17870, 19870-19874, and 21408-21409. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3201.

[0289] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 900-920, 2762-2793, 6851-6880, 9092-9112, 11276-11300, 13568-13585, 15689-15707, 17871-17900, 19875-19898, and 21410-21425. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3301.

[0290] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 921-955, 2794-2851, 6881-6935, 9113-9164, 11301-11346, 13586-13619, 15708-15742, 17901-17964, 19899-19933, and 21426-21459. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A3303.

[0291] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 956-997, 2852-2908, 6936-6986, 9165-9228, 11347-11410, 13620-13667, 15743-15785, 17965-18029, 19934-19986, and 21460-24192. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A6801.

[0292] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 998-1032, 2909-2946, 6897-7037, 9229-9292, 11411-11461, 13668-13715, 15786-15828, 18030-18068, 19987-20027, and 24193-21523. Such antigen-based vaccines can be useful in treating patients who express the HLA allele A6802.

[0293] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1033-1050, 2947-2969, 7038-7065, 9293-9312, 11462-11485, 13716-13738, 15829-15849, 18069-18091, 20028-20038, and 21524-21540. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B0702.

[0294] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1051-1066, 2970-2984, 7066-7078, 9313-9325, 11486-11497, 13739-13752, 15850-15862, 18092-18112, 20039-20051, and 21541-21549. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B0801.

[0295] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1067-1080, 2985-2999, 7079-7095, 9326-9347, 11498-11516, 13753-13767, 15863-15875, 18113-18128, 20052-20062, and 21550-21557. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1301.

[0296] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1081-1117, 3000-3052, 7096-7140, 9348-9406, 11517-11557, 13768-13821, 15876-15923, 18129-18178, 20063-20093, and 21558-21593. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1302.

[0297] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1118-1125, 3053-3058, 7141-7145, 9407-9411, 11558-11562, 13822-13827, 15924-15931, 18179-18185, 20094-20098, and 21594-21599. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1401.

[0298] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1126-1139, 3059-3070, 7146-7159, 9412-9418, 11563-11574, 13828-13837, 15932-15943, 18186-18197, 20099-20109, and 21600-21606. Such antigen-based vaccines can be useful in treating patients who express HLA allele B1402.

[0299] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1140-1192, 3071-3111, 7160-7211, 9419-9481, 11575-11633, 13838-13895, 15944-16001, 18198-18259, 20110-20141, and 21607-21635. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1501.

[0300] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1193-1220, 3112-3135, 7212-7247, 9482-9501, 11634-11670, 13896-13937, 16002-16036, 18260-18300, 20142-20165, and 21636-21656. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1502.

[0301] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1221-1245, 3136-3152, 7248-7273, 9502-9526, 11671-11693, 13938-13968, 16037-16065, 18301-18324, 20166-20179, and 21657-21669. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1503.

[0302] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1246-1266, 3153-3178, 7274-7296, 9527-9548, 11694-11722, 13969-13995, 16066-16083, 18325-18352, 20180-20200, and 21670-21689. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1510.

[0303] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1267-1270, 3179-3183, 7297-7300, 9549-9551, 11723-11725, 13996-14005, 16084-16091, 18353-18358, 20201-20205, and 21690-21692. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1513.

[0304] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1271-1286, 3184-3203, 7301-7328, 9552-9565, 11726-11742, 14006-14024, 16092-16107, 18359-18375, 20206-20224, and 21693-21705. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B1801.

[0305] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1287-1304, 3204-3225, 7329-7355, 9566-9594, 11743-11756, 14025-14048, 16108-16135, 18376-18408, 20225-20241, and 21706-21716. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B2702.

[0306] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1305-1319, 3226-3234, 7356-7370, 9595-9610, 11757-11771, 14049-14063, 16136-16145, 18409-18422, 20242-20254, and 21717-21723. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B2705.

[0307] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1320-1338, 3235-3260, 7371-7405, 9611-9641, 11772-11812, 14064-14095, 16146-16186, 18423-18463, 20255-20279, and 21724-21745. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3501.

[0308] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1339-1349, 3261-3272, 7406-7424, 9642-9661, 11813-11833, 14096-14112, 16187-16205, 18464-18482, 20280-20291, and 21746-21754. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3502.

[0309] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1350-1373, 3273-3298, 7425-7457, 9662-9697, 11834-11877, 14113-14148, 16206-16238, 18483-18513, 20292-20316, and 21755-21772. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3503.

[0310] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1374-1386, 3299-3309, 7458-7477, 9698-9719, 11878-11899, 14149-14166, 16239-16256, 18514-18538, 20317-20331, and 21773-21786. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3508.

[0311] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1387-1405, 3310-3326, 7478-7498, 9720-9744, 11900-11930, 14167-14185, 16257-16280, 18539-18560, 20332-20344, and 21787-21799. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3512.

[0312] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1406-1425, 3327-3338, 7499-7512, 9745-9757, 11931-11944, 14186-14196, 16281-16291, 18561-18572, 20345-20359, and 21800-21808. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3701.

[0313] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1426-1451, 3339-3367, 7513-7533, 9758-9782, 11945-11970, 14197-14219, 16292-16310, 18573-18599, 20360-20381, and 21809-21828. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3801.

[0314] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1452-1476, 3368-3391, 7534-7551, 9783-9802, 11971-11992, 14220-14242, 16311-16323, 18600-18619, 20382-20395, and 21829-21844. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3901.

[0315] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1477-1499, 3392-3423, 7552-7571, 9803-9831, 11993-12020, 14243-14277, 16324-16349, 18620-18653, 20396-20411, and 21845-21861. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B3906.

[0316] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1500-1527, 3424-3458, 7572-7614, 9832-9867, 12021-12057, 14278-14309, 16350-16384, 18654-18686, 20412-20431, and 21862-21888. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B4001.

[0317] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1528-1576, 3459-3497, 7615-7665, 9868-9913, 12058-12110, 14310-14359, 16385-16431, 18687-18736, 20432-20460, and 21889-21924. Such antigen-based vaccines can be useful in treating patients who express the HLA allele B4002.

[0318] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1577-1593, 3498-3517, 7666-7689, 9914-9942, 12111-12136, 14360-14380, 16432-16463, 18737-18759, 20461-20479, and 21925-21940. Such antigen-based vaccines can be useful in treating patients who express HLA allele B4006.

[0319] In certain embodiments, the one or more HIV epitope sequences selected for inclusion in an antigen-based vaccine or one or more HIV epitope sequences encoded by an HIV epitope coding sequence can include any of SEQ ID NOs: 1594-1642, 3518-3554, 7690-7742, 9943-9988, 12137-12175, 14381-14429, 16437-16510, ...

Claims

1. 1. A composition for delivering an antigen expression system, the antigen expression system comprising: A vector backbone comprising a chimpanzee adenovirus vector, optionally a ChAdV68 vector, or an alphavirus vector, optionally a Venezuelan equine encephalitis virus vector. wherein the vector backbone comprises at least one HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope-encoding nucleic acid sequence, optionally wherein the MHC class I epitope-encoding nucleic acid sequence encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

2. 2. The composition of claim 1, wherein the at least one HIV epitope is selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

3. 3. The composition of claim 1 or 2, wherein the antigen expression system comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences, each HIV MHC class I antigen-encoding nucleic acid sequence comprising an MHC class I epitope encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

4. 4. The composition of claim 3, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence that encodes an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

5. 1. A composition for delivering one or more antigens, comprising one or more HIV MHC class I antigens or one or more nucleic acid sequences encoding one or more HIV MHC class I antigens, each HIV MHC class I antigen comprising an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

6. 6. The composition of claim 5, wherein each HIV MHC class I antigen comprises an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

7. 7. The composition of claim 5 or 6, wherein the composition comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigens, each HIV MHC class I antigen comprising an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

8. 8. The composition of claim 7, wherein each HIV MHC class I antigen comprises an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4113, 4114, 4115, 4427, 4439, 4494, 4495, 4545, 4561, 4956, 4968, 4975, 4982, 5259, 5261, 5459, 5460, 5610, 5643, and 5661.

9. The MHC class I epitope (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens will be presented by one or more of the MHC proteins, said set of numerical likelihoods being determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on the set of numerical likelihoods to generate a set of selected antigens used to generate MHC class I epitopes; The composition of any one of claims 1 to 8, selected by carrying out the steps of:

10. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least one HIV MHC class I antigen-encoding nucleic acid sequence, (A) an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 22349; (B) optionally, a 5' linker sequence; and (C) optionally, a 3' linker sequence; the at least one HIV MHC class I antigen-encoding nucleic acid sequence comprising: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 151) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

11. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-2165; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 152) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

12. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166-4106; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 153) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

13. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 154) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

14. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242-8389; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 155) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

15. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930-10626; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 156) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

16. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 157) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

17. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811-15079; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 158) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

18. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope selected from the group consisting of the epitope sequences of any one of SEQ ID NOs: 15080-17174; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 159) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

19. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175-19388; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 160) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

20. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389-21003; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 161) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

21. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) at least one promoter nucleotide sequence; (ii) at least one polyadenylation (poly(A)) sequence; and the vector backbone comprising: (b) an antigen cassette, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, wherein each HIV MHC class I antigen-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence encoding at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004-22349; each of said HIV MHC class I antigen-encoding nucleic acid sequences comprising: (A) optionally, a 5' linker sequence; and (B) optionally, a 3' linker sequence; The HIV MHC class I antigen-encoding nucleic acid sequence further comprises: and the at least one antigen-encoding nucleic acid sequence comprising: (ii) optionally, a second promoter nucleotide sequence operably linked to the antigen-encoding nucleic acid sequence; and (iii) optionally at least one MHC class II antigen-encoding nucleic acid sequence; and (iv) optionally, at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 162) amino acid linker sequence; and (v) optionally at least one second poly(A) sequence, which may be a native poly(A) sequence or a poly(A) sequence exogenous to said vector backbone; The antigen cassette comprising: The composition comprising:

22. 1. A composition for delivering an antigen expression system comprising one or more vectors, said one or more vectors comprising: (a) a vector backbone, (i) a chimpanzee adenovirus vector, which is optionally a ChAdV68 vector, or an alphavirus vector, which is optionally a Venezuelan equine encephalitis virus vector; (ii) a 26S promoter nucleotide sequence; and (iii) a polyadenylation (poly(A)) sequence; the vector backbone comprising: (b) an antigen cassette integrated between the 26S promoter nucleotide sequence and the poly(A) sequence, (i) at least one antigen-encoding nucleic acid sequence, (I) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 HIV MHC class I antigen-encoding nucleic acid sequences linearly linked to each other, each of which comprises: (A) an MHC class I epitope-encoding nucleic acid sequence encoding an MHC class I epitope of 7 to 15 amino acids in length, wherein at least one of the MHC class I epitopes is selected from the group consisting of an epitope sequence from any one of SEQ ID NOs: 325 to 22349; (B) a 5' linker sequence encoding the native N-terminal amino acid sequence of the MHC class I epitope, encoding a peptide that is at least 3 amino acids in length; (C) a 3' linker sequence encoding the native C-terminal amino acid sequence of the MHC class I epitope and encoding a peptide that is at least 3 amino acids in length; Including, the HIV MHC class I antigen-encoding nucleic acid sequence, wherein the antigen cassette is operably linked to the 26S promoter nucleotide sequence, each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide having a length of 13 to 25 amino acids, and the 3' end of each MHC class I antigen-encoding nucleic acid sequence, except for the last MHC class I antigen-encoding nucleic acid sequence in the antigen cassette, is linked to the 5' end of the subsequent MHC class I antigen-encoding nucleic acid sequence. and the at least one antigen-encoding nucleic acid sequence comprising: (ii) at least two MHC class II antigen-encoding nucleic acid sequences, (I) a PADRE MHC class II sequence; and (II) a tetanus toxoid MHC class II sequence; and (III) a first nucleic acid sequence encoding a GPGPG (SEQ ID NO: 163) amino acid linker sequence connecting the PADRE MHC class II sequence to the tetanus toxoid MHC class II sequence; and (IV) a second nucleic acid sequence encoding a GPGPG (SEQ ID NO: 164) amino acid linker sequence that connects the 5' ends of the at least two MHC class II antigen-encoding nucleic acid sequences to the HIV MHC class I antigen-encoding nucleic acid sequence; (V) optionally, a third nucleic acid sequence encoding a GPGPG (SEQ ID NO: 165) amino acid linker sequence at the 3' ends of the at least two MHC class II antigen-encoding nucleic acid sequences; and and the at least two MHC class II antigen-encoding nucleic acid sequences comprising: The antigen cassette comprising: The composition comprising:

23. The ordered sequence of each element of the antigen cassette, from 5' to 3', is as follows: P ａ -(L5 ｂ -N ｃ -L3 ｄ ) Ｘ -(G5 ｅ -U ｆ ) Ｙ -G3 ｇ wherein P comprises the second promoter nucleotide sequence, and a=0 or 1; N comprises one of the MHC class I epitope-encoding nucleic acid sequences, where c=1; L5 comprises the 5' linker sequence, where b=0 or 1; L3 comprises the 3' linker sequence, where d=0 or 1; G5 comprises one of said at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 166) amino acid linker, where e=0 or 1; G3 comprises one of said at least one nucleic acid sequence encoding a GPGPG (SEQ ID NO: 167) amino acid linker, where g=0 or 1; U comprises one of the at least one MHC class II antigen-encoding nucleic acid sequence, where f=1; X=1 to 400, where for each X, the corresponding N ｃ is an epitope-encoding nucleic acid sequence, Y=0, 1, or 2, where for each Y, the corresponding U ｆ is an antigen-encoding nucleic acid sequence] 22. The composition of any of claims 10 to 21, described by a formula comprising:

24. For each X, the corresponding N ｃ 23. The composition of claim 22, wherein the are different MHC class I epitope-encoding nucleic acid sequences.

25. For each Y, the corresponding U ｆ 25. The composition of claim 22 or 24, wherein are different MHC class II antigen-encoding nucleic acid sequences.

26. a=0, b=1, d=1, e=1, g=1, h=1, X=20, Y=2, the at least one promoter nucleotide sequence is a single 26S promoter nucleotide sequence provided by the backbone; the at least one polyadenylated poly(A) sequence is a poly(A) sequence of at least 100 consecutive A nucleotides (SEQ ID NO: 168) provided by the backbone; each N encodes an MHC class I epitope 7 to 15 amino acids in length; L5 is a natural 5' linker sequence encoding the natural N-terminal amino acid sequence of the MHC I epitope, the 5' linker sequence encoding a peptide that is at least 3 amino acids in length; L3 is a natural 3' linker sequence encoding a natural terminal nucleic acid sequence of said MHC I epitope, said 3' linker sequence encoding a peptide that is at least 3 amino acids in length; U is each of the PADRE class II sequence and the tetanus toxoid MHC class II sequence; the vector backbone comprises a chimpanzee adenovirus vector, optionally a ChAdV68 vector, or an alphavirus vector, optionally a Venezuelan equine encephalitis virus vector; each of said MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide 13 to 25 amino acids in length; The composition according to any one of claims 22 to 25.

27. 10. The composition of any preceding claim, further comprising a nanoparticulate delivery vehicle.

28. 28. The composition of claim 27, wherein the nanoparticulate delivery vehicle is a lipid nanoparticle (LNP).

29. 29. The composition of claim 28, wherein the LNP comprises an ionizable amino lipid.

30. 30. The composition of claim 29, wherein the ionizable amino lipid comprises an MC3-like (dilinoleylmethyl-4-dimethylaminobutyrate) molecule.

31. The composition of any of claims 27 to 30, wherein the nanoparticle delivery vehicle encapsulates an antigen expression system.

32. 32. The composition of any one of claims 10 to 21, 23 to 25, or 27 to 31, wherein the antigen cassette is integrated between the at least one promoter nucleotide sequence and the at least one poly(A) sequence.

33. 33. The composition of any one of claims 10-21, 23-25, or 27-32, wherein the at least one promoter nucleotide sequence is operably linked to the antigen-encoding nucleic acid sequence.

34. 34. The composition of any one of claims 10-21, 23-25, or 27-33, wherein the one or more vectors comprise one or more positive-strand RNA vectors.

35. 35. The composition of claim 34, wherein the one or more positive-strand RNA vectors comprise a 5'7-methylguanosine (m7g) cap.

36. 36. The composition of claim 34 or 35, wherein the one or more positive strand RNA vectors are generated by in vitro transcription.

37. 37. The composition of any one of claims 10-21, 23-25, or 27-36, wherein the one or more vectors are autonomously replicating in mammalian cells.

38. 38. The composition of any one of claims 10-21, 23-25, or 27-37, wherein the backbone comprises at least one nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus.

39. 38. The composition of any one of claims 10-21, 23-25, or 27-37, wherein the backbone comprises at least one nucleotide sequence of a Venezuelan equine encephalitis virus.

40. 40. The composition of claim 38 or 39, wherein the backbone comprises at least sequences for nonstructural protein-mediated amplification, a 26S promoter sequence, a poly(A) sequence, nonstructural protein 1 (nsP1), nsP2, nsP3, and nsP4 genes encoded by nucleotide sequences of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus.

41. 40. The composition of claim 38 or 39, wherein the backbone comprises at least a sequence for nonstructural protein-mediated amplification encoded by a nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus, a 26S promoter sequence, and a poly(A) sequence.

42. The composition of claim 40 or 41, wherein the sequence for non-structural protein-mediated amplification is selected from the group consisting of an alphavirus 5'UTR, a 51-nt CSE, a 24-nt CSE, a 26S subgenomic promoter sequence, a 19-nt CSE, an alphavirus 3'UTR, or a combination thereof.

43. 43. The composition of any one of claims 40 to 42, wherein the scaffold does not encode the structural virion proteins capsid E2 and E1.

44. 44. The composition of claim 43, wherein the antigen cassette is inserted in place of a structural virion protein within the nucleotide sequence of Aura virus, Fort Morgan virus, Venezuelan equine encephalitis virus, Ross River virus, Semliki Forest virus, Sindbis virus, or Mayaro virus.

45. 40. The composition of claim 38 or 39, wherein the Venezuelan equine encephalitis virus comprises the sequence set forth in SEQ ID NO:3 or SEQ ID NO:

5.

46. 40. The composition of claim 38 or 39, wherein the Venezuelan equine encephalitis virus comprises the sequence of SEQ ID NO: 3 or SEQ ID NO: 5, further comprising a deletion between base pairs 7544 and 11175.

47. 47. The composition of claim 46, wherein the backbone comprises the sequence set forth in SEQ ID NO:6 or SEQ ID NO:

7.

48. 48. The composition of claim 46 or 47, wherein the antigen cassette is inserted at position 7544 to replace the deletion between base pairs 7544 and 11175 set forth in the sequence of SEQ ID NO: 3 or SEQ ID NO:

5.

49. 49. The composition of claims 44 to 48, wherein insertion of the antigen cassette results in transcription of a polycistronic RNA comprising the nsP1-4 genes and the at least one antigen-encoding nucleic acid sequence, and wherein the nsP1-4 genes and the at least one antigen-encoding nucleic acid sequence are in separate open reading frames.

50. 38. The composition of any one of claims 10-21, 23-25, or 27-37, wherein the backbone comprises at least one nucleotide sequence of a chimpanzee adenoviral vector.

51. 51. The composition of claim 50, wherein the chimpanzee adenoviral vector is a ChAdV68 vector.

52. 52. The composition of any one of claims 10-21, 23-25, or 27-51, wherein the at least one promoter nucleotide sequence is the native 26S promoter nucleotide sequence encoded by the backbone.

53. 52. The composition of any one of claims 10-21, 23-25, or 27-51, wherein the at least one promoter nucleotide sequence is an exogenous RNA promoter.

54. 54. The composition of any one of claims 10-21, 23-25, or 27-53, wherein the second promoter nucleotide sequence is a 26S promoter nucleotide sequence.

55. 54. The composition of any one of claims 10-21, 23-25, or 27-53, wherein the second promoter nucleotide sequence comprises multiple 26S promoter nucleotide sequences, each 26S promoter nucleotide sequence directing transcription of one or more of the separate open reading frames.

56. 56. The composition of any one of claims 10 to 55, wherein the one or more vectors are each at least 300 nt in size.

57. 57. The composition of any one of claims 10 to 56, wherein the one or more vectors are each at least 1 kb in size.

58. 58. The composition of claims 10-57, wherein the one or more vectors are each 2 kb in size.

59. 59. The composition of any one of claims 10 to 58, wherein the one or more vectors are each less than 5 kb in size.

60. 60. The composition of any one of claims 10 to 59, wherein at least one of the at least one antigen-encoding nucleic acid sequences encodes a polypeptide sequence or a portion thereof that is presented by an MHC class I protein.

61. 61. The composition of any one of claims 10-21, 23-25, or 27-60, wherein each antigen-encoding nucleic acid sequence is directly linked to each other.

62. 62. The composition of any one of claims 10-21, 23-25, or 27-61, wherein at least one of the at least one antigen-encoding nucleic acid sequence is linked to a different antigen-encoding nucleic acid sequence by a nucleic acid sequence encoding a linker.

63. 63. The composition of claim 62, wherein the linker links two MHC class I epitope sequences or one MHC class I epitope sequence to one MHC class II sequence.

64. 64. The composition of claim 63, wherein the linker is selected from the group consisting of: (1) a stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive glycine residues (SEQ ID NO: 169), (2) a stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 consecutive alanine residues (SEQ ID NO: 170), (3) two arginine residues (RR), (4) alanine, alanine, tyrosine (AAY), (5) a consensus sequence at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues in length that is efficiently processed by the mammalian proteasome, and (6) one or more naturally occurring sequences flanking an antigen from a cognate source protein and at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 2-20 amino acid residues in length.

65. 63. The composition of claim 62, wherein the linker links two MHC class II sequences or one MHC class II sequence to one MHC class I epitope sequence.

66. 65. The composition of claim 64, wherein the linker comprises the sequence GPGPG (SEQ ID NO: 171).

67. 67. The composition of any one of claims 10-21, 23-25, or 27-66, wherein at least one of the at least one antigen-encoding nucleic acid sequences is operably or directly linked to a separate or contiguous sequence that improves expression, stability, cellular trafficking, processing and presentation, and / or immunogenicity of the at least one antigen-encoding nucleic acid sequence.

68. The composition of claim 67, wherein the separated or consecutive sequences comprise at least one of a ubiquitin sequence, a ubiquitin sequence modified to enhance proteasome targeting (e.g., a ubiquitin sequence containing a Gly→Ala substitution at position 76), an immunoglobulin signal sequence (e.g., IgK), a major histocompatibility class I sequence, a lysosomal-associated membrane protein (LAMP)-1, a human dendritic cell lysosomal-associated membrane protein, and a major histocompatibility class II sequence, and optionally, the ubiquitin sequence modified to enhance proteasome targeting is A76.

69. 69. The composition of any one of claims 10-21, 23-25, or 27-68, wherein the at least one antigen-encoding nucleic acid sequence comprises at least 2-10, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleic acid sequences.

70. 69. The composition of any one of claims 1-3, 10-21, 23-25, or 27-68, wherein the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 15-20, 11-100, 11-200, 11-300, 11-400, or up to 400 nucleic acid sequences.

71. 69. The composition of any one of claims 1-3, 10-21, 23-25, or 27-68, wherein the at least one HIV MHC class I antigen-encoding nucleic acid sequence or the at least one antigen-encoding nucleic acid sequence comprises at least 2-400 nucleic acid sequences, and at least two of the antigen-encoding nucleic acid sequences encode a polypeptide sequence or a portion thereof that is presented by an MHC class I protein.

72. 27. The composition of claim 22 or 26, wherein at least two of the antigen-encoding nucleic acid sequences encode a polypeptide sequence or portion thereof that is presented by an MHC class I protein.

73. 10. The composition of any preceding claim, wherein when administered to the subject and translated, at least one of the antigens encoded by the at least one HIV MHC class I antigen-encoding nucleic acid or the at least one of the MHC class I epitopes is presented on antigen-presenting cells to result in an immune response.

74. 74. The composition of any one of claims 1-3 or 10-73, wherein the at least one HIV MHC class I antigen-encoding nucleic acid sequence, when administered to the subject and translated, causes at least one of the antigens to be presented on antigen-presenting cells to result in an immune response, and optionally, expression of each of the at least one antigen-encoding nucleic acid sequence is driven by the at least one promoter nucleotide sequence.

75. 75. The composition of any one of claims 1-3, or 10-74, wherein each MHC class I antigen-encoding nucleic acid sequence encodes a polypeptide sequence that is 8 to 35 amino acids in length, optionally 9-17, 9-25, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 amino acids in length.

76. 76. The composition of any one of claims 10-21, 23-25, or 27-75, wherein the at least one MHC class II antigen-encoding nucleic acid sequence is present.

77. 77. The composition of any one of claims 10-21, 23-25, or 27-76, wherein the at least one MHC class II antigen-encoding nucleic acid sequence is 12-20, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 20-40 amino acids in length.

78. 78. The composition of any one of claims 10-21, 23-25, or 27-77, wherein the at least one MHC class II antigen-encoding nucleic acid sequence is present and comprises at least one universal MHC class II antigen-encoding nucleic acid sequence, optionally wherein the at least one universal sequence comprises at least one of tetanus toxoid and PADRE.

79. 79. The composition of any one of claims 10-21, 23-25, or 27-78, wherein the at least one promoter nucleotide sequence or the second promoter nucleotide sequence is inducible.

80. 79. The composition of any one of claims 10-21, 23-25, or 27-78, wherein the at least one promoter nucleotide sequence or the second promoter nucleotide sequence is non-inducible.

81. 81. The composition of any one of claims 10-21, 23-25, or 27-80, wherein the at least one poly(A) sequence comprises a poly(A) sequence that is native to the backbone.

82. 81. The composition of any one of claims 10-21, 23-25, or 27-80, wherein the at least one poly(A) sequence comprises a poly(A) sequence that is exogenous to the backbone.

83. 83. The composition of any one of claims 10-21, 23-25, or 27-82, wherein the at least one poly(A) sequence is operably linked to at least one of the at least one antigen-encoding nucleic acid sequences.

84. 84. The composition of any one of claims 10-21, 23-25, or 27-83, wherein the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides (SEQ ID NO: 172).

85. 84. The composition of any one of claims 10-21, 23-25, or 27-83, wherein the at least one poly(A) sequence is at least 100 consecutive A nucleotides (SEQ ID NO: 173).

86. 86. The composition of any one of claims 1-3 or 10-85, wherein the antigen expression system further comprises at least one of an intron sequence, a woodchuck hepatitis virus post-transcriptional regulator (WPRE) sequence, an internal ribosome entry sequence (IRES) sequence, a nucleotide sequence encoding a 2A self-cleaving peptide sequence, a nucleotide sequence encoding a furin cleavage site, or a sequence within the 5' or 3' non-coding region known to improve mRNA nuclear transport, stability, or translation efficiency operably linked to at least one of the at least one antigen-encoding nucleic acid sequence.

87. 87. The composition of any one of claims 1-3 or 10-86, wherein the antigen expression system further comprises a reporter gene, including but not limited to, green fluorescent protein (GFP), a GFP mutant, secreted alkaline phosphatase, luciferase, a luciferase mutant, or a detectable peptide or epitope.

88. 88. The composition of claim 87, wherein the detectable peptide or epitope is selected from the group consisting of an HA tag, a Flag tag, a His tag, or a V5 tag.

89. the at least one MHC class I antigen-encoding nucleic acid sequence comprising: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens is presented by one or more of said MHC proteins, said set of numerical likelihoods being determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on said set of numerical likelihoods to generate a set of selected antigens used to generate said at least one MHC class I antigen-encoding nucleic acid sequence; The composition of any one of claims 10 to 21, 23 to 25, or 27 to 75, selected by performing the steps of:

90. each of said MHC class I epitope-encoding nucleic acid sequences comprising: (a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing, wherein the nucleotide sequencing data is used to obtain data representing each peptide sequence of a set of antigens; (b) inputting the peptide sequence of each antigen into a presentation model to generate a set of numerical likelihoods that each of the antigens will be presented by one or more MHC proteins, said set of numerical likelihoods being determined based at least on the received mass spectrometry data; (c) selecting a subset of the set of antigens based on said set of numerical likelihoods to generate a set of selected antigens used to generate said at least 20 MHC class I antigen-encoding nucleic acid sequences; 27. The composition of claim 22 or 26, selected by performing the steps of:

91. 91. The composition of claim 9, 89, or 90, wherein the number of sets of selected antigens is between 2 and 20.

92. The presentation model: (a) the presence of a pair of a particular one of the MHC alleles and a particular amino acid at a particular position in the peptide sequence; (b) the likelihood of presentation of such peptide sequences comprising said particular amino acids at said particular positions by said particular one of said MHC alleles of said pair; The composition according to claim 9 or 89 to 91, which expresses a dependency between

93. 93. The composition of claims 9 or 89-92, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being presented relative to antigens not selected based on the presentation model, and optionally the selected antigens have been validated as being presented by one or more specific MHC alleles.

94. 94. The composition of claims 9 or 89-93, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being able to induce an immune response in response to the presence of HIV in the subject, relative to antigens not selected based on the presentation model.

95. 95. The composition of claim 9 or 89-94, wherein selecting the set of selected antigens comprises selecting antigens that have an increased likelihood of being presented to naive T cells by professional antigen-presenting cells (APCs), relative to antigens not selected based on the presentation model, and optionally the APCs are dendritic cells (DCs).

96. 96. The composition of claims 9 or 89-95, wherein selecting the set of selected antigens comprises selecting antigens that have a reduced likelihood of being inhibited by central or peripheral tolerance relative to antigens not selected based on the presentation model.

97. 97. The composition of claims 9 or 89-96, wherein selecting the set of selected antigens comprises selecting antigens that have a reduced likelihood of being able to induce an autoimmune response against normal tissue in the subject, relative to antigens not selected based on the presentation model.

98. 98. The composition of claim 9 or 89-97, wherein the exome or transcriptome nucleotide sequencing data is obtained by performing next generation sequencing (NGS) or any massively parallel sequencing approach.

99. 99. The composition of any one of claims 1 to 3 or 10 to 98, wherein the antigen cassette comprises a junction epitope sequence formed by adjacent sequences within the antigen cassette.

100. 100. The composition of claim 99, wherein the or each junction epitope sequence has an affinity for MHC greater than 500 nM.

101. 101. The composition of claim 99 or 100, wherein each junction epitope sequence is non-self.

102. 10. A composition according to any preceding claim, wherein each of said MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele present in at least 5% of the population.

103. 10. The composition of any preceding claim, wherein each of the MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA prevalence in the population of at least 0.01%.

104. 10. The composition of any preceding claim, wherein each of the MHC class I epitopes is predicted or verified to be presentable by at least one HLA allele, and each antigen / HLA pair has an antigen / HLA abundance in the population of at least 0.1%.

105. A pharmaceutical composition comprising the composition of any of the preceding claims and a pharmaceutically acceptable carrier.

106. 106. The composition of claim 105, further comprising an adjuvant.

107. 1. An isolated nucleotide sequence or set of isolated nucleotide sequences comprising an antigen cassette according to any of the preceding composition claims and one or more elements derived from the sequence of SEQ ID NO:3 or SEQ ID NO:5, wherein optionally said one or more elements are selected from the group consisting of sequences required for nonstructural protein-mediated amplification, 26S promoter nucleotide sequences, poly(A) sequences, and nsP1-4 genes of the sequence set forth in SEQ ID NO:3 or SEQ ID NO:5, and optionally said nucleotide sequences are cDNAs.

108. 108. The isolated nucleotide sequence of claim 107, wherein the sequence or set of isolated nucleotide sequences comprises an antigen cassette described in any of the preceding composition claims inserted at position 7544 of the sequence set forth in SEQ ID NO: 6 or SEQ ID NO:

7.

109. the nucleotide sequence of a T7 or SP6 RNA polymerase promoter located 5' of said one or more elements derived from the sequence of SEQ ID NO:3 or SEQ ID NO:5; optionally, one or more restriction sites located 3' of said poly(A) sequence; 109. The isolated nucleotide sequence of claim 107 or 108, further comprising:

110. 108. The isolated nucleotide sequence of claim 107, wherein the antigen cassette of any of the preceding composition claims is inserted at position 7563 of SEQ ID NO:8 or SEQ ID NO:

9.

111. A vector or a set of vectors comprising a nucleotide sequence according to claims 107 to 110.

112. 112. An isolated cell comprising a nucleotide sequence or set of isolated nucleotide sequences according to claims 107-111, optionally wherein the cell is a BHK-21, CHO, HEK293 or mutant thereof, 911, HeLa, A549, LP-293, PER.C6, or AE1-2a cell.

113. A method for treating a subject having HIV, comprising administering to said subject a composition according to any of the preceding composition claims, or a pharmaceutical composition according to any of claims 105-106.

114. 107. A method for inducing an immune response in a subject, comprising administering to said subject a composition according to any of the preceding composition claims, or a pharmaceutical composition according to any of claims 105-106.

115. 115. The method of any of claims 113-114, wherein the subject expresses at least one HLA allele predicted or known to present at least one of the MHC class I epitopes encoded by the one or more vectors of the antigen expression system.

116. 116. The method of any of claims 113-115, wherein the composition is administered intramuscularly (IM), intradermally (ID), subcutaneously (SC), or intravenously (IV).

117. 116. The method of any of claims 113-115, wherein the composition is administered intramuscularly.

118. 118. The method of any one of claims 113 to 117, further comprising administering to the subject a second vaccine composition.

119. The method of claim 118, wherein said second vaccine composition is administered prior to administration of the composition or pharmaceutical composition of any one of claims 113-114.

120. The method of claim 118, wherein said second vaccine composition is administered subsequent to the administration of the composition or pharmaceutical composition of any one of claims 113-114.

121. The method of claim 119 or 120, wherein said second vaccine composition is the same as the composition or pharmaceutical composition of any one of claims 113-114.

122. The method of claim 119 or 120, wherein said second vaccine composition is different from the composition or pharmaceutical composition of any one of claims 113-114.

123. 123. The method of claim 122, wherein the second vaccine composition comprises a chimpanzee adenoviral vector encoding at least one antigen-encoding nucleic acid sequence.

124. 124. The method of claim 123, wherein the at least one antigen-encoding nucleic acid sequence encoded by the chimpanzee adenoviral vector is the same as the at least one antigen-encoding nucleic acid sequence described in any of the preceding composition claims.

125. A method for producing an antigen expression system according to any one of claims 1 to 4 or 10 to 106, comprising the steps of: (a) obtaining a linearized DNA sequence comprising the backbone and the antigen cassette; (b) in vitro transcribing the linearized DNA sequence by adding the linearized DNA sequence to an in vitro transcription reaction containing all components necessary for transcribing the linearized DNA sequence into RNA, optionally further comprising in vitro addition of the m7g cap to the resulting RNA; (c) isolating the one or more vectors from the in vitro transcription reaction; and The method comprising:

126. 126. The method of claim 125, wherein the linearized DNA sequence is generated by linearizing a DNA plasmid sequence or by amplification using PCR.

127. 127. The method of claim 126, wherein the DNA plasmid sequence is generated using one of bacterial recombination or total genomic DNA synthesis or total genomic DNA synthesis with amplification of DNA synthesized within a bacterial cell.

128. 126. The method of claim 125, wherein isolating the one or more vectors from the in vitro transcription reaction involves one or more of phenol-chloroform extraction, silica column-based purification, or similar RNA purification methods.

129. 107. A method for producing a composition according to any one of claims 1 to 4 or 10 to 106 for delivering said antigen expression system, comprising the steps of: (a) providing a nanoparticulate delivery vehicle component; (b) providing said antigen expression system; (c) providing conditions sufficient for the formation of the nanoparticulate delivery vehicle and the antigen expression system, said composition for delivering said antigen expression system; and The method comprising:

130. 130. The method of claim 129, wherein the conditions are provided by microfluidic mixing.

131. 1. A method of assessing a subject for HIV, comprising: a) determining, or having already determined, the HIV subtype of the subject's HIV; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence selected from the group consisting of epitope sequences from any one of SEQ ID NOs: 325 to 22349; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

132. 132. The method of claim 131, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Tables 35-45.

133. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype A1; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-2165; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

134. 134. The method of claim 133, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 35.

135. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype A2; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166-4106; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

136. 136. The method of claim 135, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 36.

137. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype B; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

138. 138. The method of claim 137, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 37.

139. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype C; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242-8389; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

140. 140. The method of claim 139, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 38.

141. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype D; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930-10626; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

142. 142. The method of claim 141, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 39.

143. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F1; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

144. 144. The method of claim 143, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 40.

145. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype F2; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811 to 15079; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

146. 146. The method of claim 145, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 41.

147. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype G; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080-17174; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

148. 148. The method of claim 147, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 42.

149. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype H; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175-19388; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

150. 150. The method of claim 149, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 43.

151. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype J; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389-21003; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

152. 152. The method of claim 151, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 44.

153. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject's HIV is HIV subtype K; b) determining, or having previously determined, whether the subject expresses HLA alleles predicted or known to present MHC class I epitopes encoded by antigen-encoding nucleic acid sequences in an antigen-based vaccine; c) determining, or having previously determined, whether the subject is a candidate for treatment with the antigen-based vaccine if the subject expresses the HLA allele and the HIV subtype expresses the MHC class I epitope encoded by the antigen-encoding nucleic acid sequence in the antigen-based vaccine; The MHC class I epitope comprises at least one MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349; d) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

154. 154. The method of claim 153, wherein the HLA alleles expressed by the subject are selected from the group consisting of the HLA alleles of Table 45.

155. 155. The method of any of claims 131 to 154, wherein determining or having already determined the HIV subtype of the HIV in the subject comprises obtaining a dataset indicative of the HIV subtype from a third party that processed a sample from the subject.

156. 155. The method of any of claims 131 to 154, wherein determining whether the subject expresses an HLA allele, or having already determined it, comprises obtaining a dataset from a third party that processed a sample from the subject.

157. 155. The method of any of claims 131-154, wherein determining whether the subject expresses an HLA allele, or has already determined it, comprises obtaining a sample from the subject and assaying the sample using a method selected from the group consisting of exome sequencing, targeted exome sequencing, transcriptome sequencing, Sanger sequencing, PCR-based genotyping assays, mass spectrometry-based methods, microarrays, nanostrings, ISH, and IHC.

158. 158. The method of claim 157, wherein the sample is selected from tissue, body fluid, blood, spinal fluid, or fine needle aspirate.

159. 159. The method of any of claims 131 to 158, wherein the HLA allele has an HLA frequency of at least 1%.

160. 1. A method for treating a subject, comprising administering to said subject an antigen-based vaccine, said antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

161. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-2165.

162. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166-4106.

163. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241.

164. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242-8389.

165. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930-10626.

166. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810.

167. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811-15079.

168. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080-17174.

169. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175-19388.

170. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389-21003.

171. 1. A method of treating a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004-22349.

172. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-22349.

173. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325-2165.

174. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype A2; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166-4106.

175. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype B, or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107-6241.

176. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype C; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242-8389.

177. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype D; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence selected from the group consisting of the epitope sequences of any one of SEQ ID NOs: 8930 to 10626.

178. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F1; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627-12810.

179. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype F2; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811-15079.

180. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype G; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises at least one HIV epitope sequence selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080-17174.

181. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype H; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175-19388.

182. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype J; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389-21003.

183. 1. A method for inducing an immune response in a subject having HIV, comprising administering to the subject an antigen-based vaccine, the antigen-based vaccine comprising: 1) at least one MHC class I epitope expressed by an HIV subtype that is HIV subtype K; or 2) an MHC class I epitope-encoding nucleic acid sequence encoding said at least one MHC class I epitope; wherein the at least one MHC class I epitope comprises an MHC class I epitope sequence comprising at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004-22349.

184. 184. The method of any of claims 160-183, wherein the subject expresses at least one HLA allele predicted or known to present said at least one MHC class I epitope sequence.

185. determining that the subject is a candidate for receiving the antigen-based vaccine prior to administering the antigen-based vaccine to the subject; and wherein said determining further comprises: 1) the subject expresses an HLA allele known or predicted to present the at least one MHC class I epitope; and 2) the subject has been exposed to or is susceptible to exposure to the HIV subtype; The method of any of claims 160 to 183, comprising identifying:

186. 186. The method of any of claims 184 or 185, wherein said at least one HLA allele is selected from the group consisting of the HLA alleles of Tables 35-45.

187. 187. The method of any of claims 131-186, wherein the antigen-based vaccine comprises an antigen expression system.

188. 188. The method of claim 187, wherein the antigen expression system comprises any one of the antigen expression systems of any one of claims 10 to 104.

189. The method of any of claims 131 to 188, wherein said antigen-based vaccine comprises any one of the pharmaceutical compositions of any one of claims 105 to 106.

190. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 325 to 2165.

191. The composition of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 2166 to 4106.

192. 10. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 4107 to 6241.

193. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 6242 to 8389.

194. 10. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 8930 to 10626.

195. 10. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 10627 to 12810.

196. 10. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 12811 to 15079.

197. 10. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 15080 to 17174.

198. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 17175 to 19388.

199. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 19389 to 21003.

200. The composition of any one of claims 1 to 9, wherein each MHC class I epitope comprises at least one HIV epitope selected from the group consisting of the sequences set forth in SEQ ID NOs: 21004 to 22349.

201. 1. A method of assessing a subject for HIV, comprising: a) determining, or having previously determined, that the subject expresses an HLA allele; b) obtaining or having obtained sequencing data for HIV present in said subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325-22349, and a second candidate epitope sequence is a variant epitope sequence, each of the first and second candidate epitope sequences predicted to be presented by the HLA allele expressed by the subject; d) generating said antigen-based vaccine comprising said selected candidate epitope sequences; e) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

202. 1. A method for treating a subject having HIV, comprising: a) determining, or having previously determined, that the subject expresses an HLA allele; b) obtaining or having obtained sequencing data for HIV present in said subject; c) selecting candidate epitope sequences for inclusion in an antigen-based vaccine, wherein a first candidate epitope sequence comprises at least one HIV epitope selected from the group consisting of sequences set forth in SEQ ID NOs: 325-22349, and a second candidate epitope sequence is a variant epitope sequence, each of the first and second candidate epitope sequences predicted to be presented by the HLA allele expressed by the subject; d) generating said antigen-based vaccine comprising said selected candidate epitope sequences; e) optionally administering or having previously administered said antigen-based vaccine to said subject; The method comprising:

203. 202. The method of any one of claims 1 to 8 or 131 to 202, wherein the epitope sequence of any one of SEQ ID NOs: 325 to 22349 is identified by applying a presentation model trained on HLA-presented peptides sequenced by mass spectrometry.

204. 204. The method of claim 203, wherein the proposed model exhibits a precision value of 0.28 at a recall of 40%.

205. The method of claim 203, wherein the proposed model exhibits an AUC of 0.24.

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