HIV vaccines comprising one or more population episensus antigens

A technology of HIV-1, epitope, applied in the field of HIV vaccine

Pending Publication Date: 2018-05-22
翠德国家安全有限责任公司 +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Specifically, it was found that rhesus macaques (RM) vaccinated with cytomegalovirus (CMV)-based vectors expressing Simian Immunodeficiency Virus (SIV) antigens were initially infected, but that SIV failed several stringent conditions within one to two years of infection. detected by the standard

Method used

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  • HIV vaccines comprising one or more population episensus antigens
  • HIV vaccines comprising one or more population episensus antigens
  • HIV vaccines comprising one or more population episensus antigens

Examples

Experimental program
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Embodiment 1

[0084] Example 1: Graphical Model of Optimal Epitope Coverage of Aligned Sequences.

[0085] Suppose there is a set S={s of N aligned sequences 1 ,s 2 ,...,s N}. Each sequence is a string of letters (corresponding to the twenty amino acids, and possibly additionally a few special characters corresponding to gaps, unknowns, etc.). Due to sequence alignment, all sequences have the same length T, position t=1...T is well defined from sequence to sequence; s n [t] will be written as the tth character in the nth sequence. For a subsequence of s starting at position t and ending at position u, it is useful to introduce the notation s[t:u].

[0086] Potential epitopes are defined as short sequences of k characters, usually 8 to 12 characters. The epitopes studied are subsequences of the sequences in S. In fact, the sequence s can be thought of as a list of epitopes: e 1 ,...,e T-k+1 , where e t =s[t:t+k-1]. Note, however, that for a list of sequence-related epitopes, the e...

example 2

[0136] Example 2: Graphical Model for Optimal Epitope Coverage of Unaligned Sequences

[0137] Take a set of N unaligned protein sequences S={s 1 ,s 2 ,...,s N} to characterize virus variability within a target population (e.g., phylogenetic clade, national or global). A potential epitope is a subsequence of k amino acids (usually k=9). Each potential epitope e is assigned an integer frequency f(e) corresponding to the number of sequences in S in which e occurs. The monovalent problem is to design a single artificial sequence q that resembles the natural protein but optimally covers the potential epitopes in population S. Writing E(q) as the set of epitopes occurring in q, our measure of coverage is

[0138] Coverage (q) = ∑ e∈E(q) f(e) / ∑ e∈E(s) f(e)

[0139]The numerator is the sum of the frequencies of epitopes appearing in q, and the denominator is normalized by the sum of all epitopes appearing in any sequence in S. This equation can be represented as a directed g...

Embodiment 3

[0142] Example 3: Custom Therapeutic Vaccines.

[0143] While it is not possible to build a designer vaccine for each subject, the viruses from that subject can be sequenced to try to get a good match from a small benchmark set of vaccine options. The first thing to consider is the experimental population based on the US clade B, which is focused on Gag proteins. A South African-based baseline vaccine set and a global vaccine set were designed, along with an updated US-based B clade design. p24 is the most highly conserved subprotein of Gag and can be excised from the larger Gag protein to provide a conserved region approximately 230 amino acids in length. A conserved region approach has also been considered as an alternative to Gag, perhaps focusing on regions in Gag and Pol, which may include conserved segments of Nef as well as any other protein of interest.

[0144] This is a very different optimization problem than trying to design an ensemble that provides optimal popu...

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Abstract

Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memoryT cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 059,497, filed October 3, 2014, and U.S. Provisional Patent Application Serial No. 62 / 059,506, filed October 3, 2014, each of which is passed The entire contents of which are incorporated herein by reference. [0003] References to Sequence Listings Submitted Electronically [0004] The contents of the electronically filed sequence listing in the ASCII text file (name: 3525.010PC02 Seq listing_ST25.txt; size: 3,634,253 bytes; and creation date: October 5, 2015) filed with this application in its entirety adopts Incorporated herein by reference. technical field [0005] This topic relates to HIV in general and HIV vaccines in particular. Background technique [0006] In 2013, there were approximately 2.3 million new human immunodeficiency virus (HIV) infections, more than 35 million HIV-infected people, and 1.6 million acquired immu...

Claims

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Application Information

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IPC IPC(8): A61P31/18A61K39/21
CPCA61K2039/53A61K2039/70C12N2710/16143C12N2740/16034C12N2740/16234A61K39/12A61P31/18A61P37/04A61K39/21C12N15/867C12N2740/16222C12N15/86C12N2740/16334C12N2740/16322C07K2319/00
Inventor 埃里克·布鲁宁克劳斯·弗鲁赫路易斯·皮克尔贝蒂·T·M·科贝尔詹姆斯·泰勒埃米莉·马歇尔
Owner 翠德国家安全有限责任公司
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