Arenaviruses as vectors

Abstract

The present application relates to arenavirus particles containing genomes engineered to segregate arenavirus open reading frames ("ORFs") into two or more functional fragments, which are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high levels of transgene expression. In certain embodiments, the arenavirus particles are trisegmented. In particular, described herein are nucleotide sequences comprising one or more ORFs comprising nucleotide sequences encoding functional fragments of arenavirus GP, NP, L, or Z. Also described herein are arenavirus particles containing genomes engineered to segregate arenavirus ORFs into two or more functional fragments, which are expressed from two or more viral mRNA transcripts. Also described herein are arenavirus genome or antigenome segments engineered such that transcription produces one or more mRNA transcripts comprising nucleotide sequences encoding functional fragments of arenavirus GP, NP, L, or Z. The arenavirus particles described herein may be suitable for vaccines and / or disease treatment and / or for use in immunotherapy.

Description

[Technical Field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 932,214, filed November 7, 2019, the disclosure of which is incorporated herein by reference in its entirety.

[0002] (Reference to electronically submitted sequence listing) This application incorporates by reference the Sequence Listing submitted herewith as a text file entitled "Sequence_Listing_13194-050-228.TXT", which was created on November 5, 2020, has a size of 701,226 bytes.

[0003] (1. Introduction) The present application relates to arenavirus particles modified so that the arenavirus open reading frame ("ORF") is separated by two or more mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high levels of transgene expression. In certain embodiments, the arenavirus particles are trisegmented. In particular, described herein are nucleotide sequences comprising one or more ORFs comprising nucleotide sequences encoding functional fragments of arenavirus GP, NP, L, or Z. Also described herein are arenavirus particles modified so that the arenavirus ORF is separated by two or more mRNA transcripts. Also described herein are arenavirus genome or antigenome segments modified such that the transcription produces one or more mRNA transcripts comprising nucleotide sequences encoding functional fragments of arenavirus GP, NP, L, or Z. The arenavirus particles described herein may be suitable for vaccines and / or disease treatment and / or for use in immunotherapy. [Background technology]

[0004] (2.Background) 2.1 Replicating viral vector systems Replicating viral vector systems are optimally adapted for delivering a selected target antigen with the goal of inducing a strong immune response against it. Viral vector systems are particularly useful when the goal is to induce a strong CD8+ T cell response, for example, in tumor immunotherapy or to cure persistent viral infections. To serve as a viral delivery system, wild-type viruses can be redesigned to incorporate transgene sequences, enabling them to induce an immune response against the respective translation product, i.e., the selected target. Furthermore, if based on a virus that can cause a disease (known or poorly defined), the redesign should confer a defined degree of attenuation to the resulting vector. On the other hand, the immunogenicity of a viral vector delivery system is generally determined by the administered vector dose. Therefore, attenuation should not reduce viral growth in tissue culture systems to the point where industrial production becomes unfeasible. Therefore, the usefulness of a replicable vector system for medical applications is essentially determined by the following criteria:

[0005] 1) Good growth in cell culture (production yield) allowing the production of vectors to high titers in industrial fermentation processes

[0006] 2) stable attenuation, i.e., the inability of the vector to revert to wild-type (more virulent) replication behavior in the vaccinated host (genetic stability);

[0007] 3) High levels of transgene expression (transgene expression level) to induce a strong immune response against the desired target antigen.

[0008] Arenaviruses, such as lymphocytic choriomeningitis virus (LCMV) and Pikinde virus (PICV), have been redesigned to serve as unattenuated replicative delivery systems that induce immune responses against incorporated heterologous antigens (Cheng BY et al. (2015) J Virol 89, 7373-7384; Dhanwani R et al. (2015) J Virol 90, 2551-2560; Emonet SF et al. (2009) Proc Natl Acad Sci USA 106, 3473-3478; Kallert SM et al. (2017) Nat Commun 8, 15327; Popkin DL et al. (2011) J Virol 85, 7928-7932). The native arenavirus genome consists of two RNA segments, both of which contain open reading frames (ORFs) encoding glycoproteins and nucleoproteins encoded on the short (S) segment and polymerase L and matrix protein Z encoded on the large (L) segment (Figure 1A). In addition to the four arenavirus ORFs, the S segment can be duplicated to incorporate foreign transgene sequences, and the arenavirus GP and NP ORFs can be sequestered on the resulting two S segments (S). NP , S GP; Figure 1B-E; (Cheng BY et al. (2015) J Virol 89, 7373-7384; Emonet SF et al. (2009) Proc Natl Acad Sci USA 106, 3473-3478; Kallert SM et al. (2017) Nat Commun 8, 15327). The concept behind separating NP and GP on separate S segments is to allow the virus to possess three genomic RNA segments in order to maintain its complete proteome. As a result, there are four possibilities for how to position NP, GP, and two heterologous ORFs (labeled "hp" in Figure 1B-1G) on the two segments. These four possibilities are referred to here as r3LCMV, artLCMV, r3LCMVrev, and artLCMVrev (Figure 1B-E). r3LCMVrev and artLCMVrev grow to extremely low titers, much lower than r3LCMV or artLCMV (Cheng BY et al. (2015) J Virol 89, 7373-7384), and therefore do not meet criterion 1 above. The low growth of r3LCMVrev and artLCMVrev is presumably due to the NP being located near the 5' untranslated region (UTR) and therefore expressed under the control of the respective (weaker) viral promoter sequences. Therefore, the r3LCMVrev and artLCMVrev designs are not well suited for industrial production. Kallert et al. (Kallert SM et al. (2017) Nat Commun 8, 15327) further demonstrated that r3LCMV is genetically unstable: during infection of immunodeficient mice, r3LCMV underwent intersegmental RNA recombination to generate a two-segmented virus, thereby recombining the NP and GP ORFs on a single RNA segment. The resulting virus had lost (most of) its transgene and was no longer attenuated (Fig. 1F), and therefore did not meet criterion 2 above due to safety concerns. In summary, neither r3LCMV nor r3LCMVrev met all three criteria (production yield, genetic stability, transgene expression level; Fig. 2).In contrast, artLCMV remained genetically stable even after prolonged replication in immunocompromised animals. The underlying mechanistic explanation is that the NP and GP ORFs in artLCMV can recombine on a single S segment (Figure 1G), but such recombination can only occur at the expense of losing the 5'UTR and duplicating the 3'UTR at both ends of the resulting S segment. The 5'UTR and 3'UTR are known to form a noncovalent panhandle structure through RNA base pairing, which allows template recognition by the viral RNA-dependent RNA polymerase (RdRp) in both sequence- and structure-dependent manners. Therefore, accurate 5'UTR and 3'UTR sequences are required for biological activity, and deviations from the native sequence are not tolerated (Perez and de la Torre (2003) J Virol 77, 1184-1194). Therefore, the hypothetical recombinant product shown in Figure 1G would be unable to serve as a template for recognition by the viral RdRp and would be biologically inactive. artLCMV is not only genetically stable but also grows well in cell culture (Cheng BY et al. (2015) J Virol 89, 7373-7384; Kallert SM et al. (2017) Nat Commun 8, 15327; Popkin DL et al. (2011) J Virol 85, 7928-7932). Therefore, among the four strategies outlined in Figures 1B-1E, artLCMV was the only three-segmented arenavirus design that met specifications 1 and 2 above: good production yield and genetic stability ensuring safety.

[0009] 2.2 Glycoproteins and their precursors The GP open reading frame encodes three functional protein subunits that are expressed as a single ribosomal translation product. Upon insertion of the nascent polypeptide into the endoplasmic reticulum (ER), the signal peptide is cleaved from the trailing GP1 domain by a signal peptidase (Figure 3A). The remaining GP1-GP2 sequence is inserted into the membrane and is post-translationally cleaved by subtilisin kexin isozyme-1 (SKI-1) / site 1 protease (S1P, Figure 3A) to yield the GP1 and GP2 subunits, which remain noncovalently associated in the mature glycoprotein complex. Of particular note are the essential properties of arenavirus GP signal peptides (SPs): unlike most signal peptides, which are approximately 20 amino acids long and rapidly degraded after signal peptidase cleavage, arenavirus glycoprotein SPs are typically >50 amino acids long (Eichler R et al. (2003) FEBS Lett 538, 203-206), and not only play a role in inserting the GP protein into the ER but also remain associated with the GP1 / GP2 complex, which is incorporated into mature virions. Furthermore, arenavirus glycoprotein SPs also play an essential role in the posttranslational proteolytic cleavage of GP1 from GP2 by SKI-1 / S1P. When arenavirus SP was used instead of a foreign signal peptide in transient transfection experiments, the GP1 / GP2 sequence was inserted into the ER, but it was not processed by SKI-1 / S1P (Agnihothram, SS et al. (2006) J Virol 80, 5189-5198; Eichler R et al. (2003) EMBO Rep 4, 1084-1088; Schrempf S et al. (2007) J Virol 81, 12515-12524). However, GP1 / GP2 cleavage by SKI-1 / S1P is essential for the glycoprotein complex to be biologically active (Pinschewer, DD et al. (2003) Proc Natl Acad Sci USA 100, 7895-7900).

[0010] 2.3 Modified Arenavirus Particles and Arenavirus Genome Segments Recently, it has been shown that infectious arenavirus particles can be modified to contain a genome capable of amplifying and expressing its genetic material in infected cells but unable to produce further progeny in normal, unaltered cells (i.e., infectious, replication-deficient arenavirus particles) (International Publication Nos. WO 2009 / 083210 A1, WO 2014 / 140301 A1, and WO 2015 / 082570 A1). It has also been shown that modified arenavirus genome segments can be modified to carry viral ORFs at locations other than the wild-type ORF locations (International Publication No. WO 2016 / 075250 A1 and Publication No. US 2017 / 0319673 A1). It has further been shown that modified Pikindevirus genome segments can be modified to carry viral ORFs at locations other than the wild-type ORF locations (International Publication WO 2017 / 198726 A1 and Publication US 2019 / 0135875 A1).

[0011] There is a pressing need for compositions such as modified arenavirus particles and related compositions to be used in vaccines and immunotherapy for a variety of diseases. Summary of the Invention

[0012] (3. Summary of the Invention) Provided herein are nucleotide sequences, arenavirus particles, arenavirus genome or antigenome segments, and related compositions. Also provided herein are methods for making arenavirus genome or antigenome RNA segments, generating arenavirus particles, and rescuing arenavirus particles from cDNA or RNA.

[0013] 3.1 Nucleotide Sequences and Related Compositions and Methods In one aspect, provided herein is a nucleotide sequence. In some embodiments, provided herein is a nucleotide sequence comprising a first open reading frame (ORF) and a second ORF, wherein one of the two ORFs is in the sense orientation and the other ORF is in the antisense orientation; wherein the first ORF comprises a nucleotide sequence encoding a functional fragment of a first polypeptide, and the first ORF does not encode a full-length first polypeptide; wherein the second ORF is a) a second polypeptide; or b) a functional fragment of the first polypeptide, the second ORF does not encode the full-length first polypeptide; or c) a functional fragment of a second polypeptide, the second ORF does not encode a full-length second polypeptide; or d) Heterologous Non-Arenavirus Polypeptides and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenavirus GP, NP, Z, and L.

[0014] In certain embodiments, the first ORF and the second ORF are separated by an arenavirus intergenic region (IGR), and each ORF is under the control of an arenavirus 3' untranslated region (UTR) or an arenavirus 5' UTR.

[0015] In certain embodiments, the first ORF further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide; wherein the third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0016] In certain embodiments, the second ORF further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide; wherein the third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0017] In certain embodiments, the first ORF is part of a transcription unit that further comprises another ORF, wherein the other ORF and the first ORF are separated by an internal ribosome entry site (IRES). In certain embodiments, the second ORF is part of a transcription unit that further comprises another ORF, wherein the other ORF and the second ORF are separated by an IRES. In certain embodiments, the first ORF and / or the second ORF comprises a nucleotide sequence encoding an arenavirus GP signal peptide or a functional fragment thereof, and the other ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide or an arenavirus NP, Z, or L.

[0018] In certain embodiments, the arenaviruses GP, NP, Z, and L are derived from LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0019] In one embodiment, provided herein is a nucleotide sequence comprising an open reading frame (ORF), wherein the ORF comprises: a) a functional fragment of a first polypeptide, and b) a heterologous non-arenavirus polypeptide or a second polypeptide comprising a nucleotide sequence encoding wherein the ORF does not encode a full-length first polypeptide; and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenaviruses GP, NP, Z, and L that are not derived from Lassa virus. In certain embodiments, the first and second polypeptides are selected from the group consisting of arenaviruses GP, NP, Z, and L of LCMV, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Gunarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0020] In certain embodiments, the ORF is a first ORF, and the nucleotide sequence further comprises a second ORF. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a third polypeptide, a functional fragment of the first polypeptide, a functional fragment of the third polypeptide, or a second heterologous non-arenavirus polypeptide; wherein the third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; wherein one of the two ORFs is in the sense orientation and the other ORF is in the antisense orientation; wherein the second ORF does not encode the full-length first polypeptide; wherein the second ORF does not encode the full-length third polypeptide; and wherein the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide are the same as or different from each other. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a functional fragment of the first polypeptide, wherein the functional fragment encoded by the first ORF is different from the functional fragment encoded by the second ORF.

[0021] In certain embodiments, the nucleotide sequence does not further comprise a second ORF.

[0022] In certain embodiments, the nucleotide sequence is an arenavirus genome or antigenome S segment. In certain embodiments, the nucleotide sequence is an arenavirus genome or antigenome L segment.

[0023] In certain embodiments, the first ORF is under the control of the arenavirus 3' UTR and the second ORF is under the control of the arenavirus 5' UTR. In certain embodiments, the first ORF is under the control of the arenavirus 5' UTR and the second ORF is under the control of the arenavirus 3' UTR.

[0024] In certain embodiments, the first ORF comprises a nucleotide sequence encoding an arenavirus GP signal peptide, either alone or fused to a heterologous non-arenavirus polypeptide. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide; wherein the heterologous non-arenavirus polypeptide encoded by the first ORF and the heterologous non-arenavirus polypeptide encoded by the second ORF are the same as or different from each other. In certain embodiments, the first ORF is under the control of an arenavirus 3' UTR and the second ORF is under the control of an arenavirus 5' UTR.

[0025] In certain embodiments, the first ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the second ORF comprises a nucleotide sequence encoding NP. In certain embodiments, the first ORF is under the control of an arenavirus 5' UTR and the second ORF is under the control of an arenavirus 3' UTR.

[0026] In certain embodiments, the first polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95 , SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140;and the second polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO: 102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140;and the third polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO: 102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, the first polypeptide comprises an amino acid sequence identical to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134;

[0027] In some embodiments, the functional fragment of the first polypeptide is selected from the group consisting of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, SEQ ID NO: and / or SEQ ID NO:135, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, SEQ ID NO:136, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.

[0028] In certain embodiments, the functional fragment encoded by the first ORF or the second ORF is an arenavirus GP signal peptide or a functional fragment thereof.

[0029] In certain embodiments, the heterologous non-arenavirus polypeptide, the second heterologous non-arenavirus polypeptide, or both heterologous non-arenavirus polypeptides are each an antigen derived from an infectious organism, a tumor, or an allergen. In certain embodiments, the antigen is selected from the group consisting of: (a) Viral antigens. Viral antigens include those from the families Adenoviridae, Herpesviridae, Leviviridae, Orthomyxoviridae, Parvoviridae, Filoviridae, Hantaviridae, Poxviridae, Papillomaviridae, Polyomaviridae, and Paramyxoviridae. from a viral family selected from the group consisting of: Pneumoviridae, Picornaviridae, Reoviridae, Retroviridae, Flaviviridae, Hepadnaviridae, Togaviridae, Rhabdoviridae, Arenaviridae, and Coronaviridae; (b) Bacterial antigens. Bacterial antigens include those from the Aquaspirillum family, Azospirillum family, Azotobacteraceae family, Bacteroidaceae family, Bartonellaceae family, Bdellovibrio family, Campylobacteraceae family, Chlamydiaceae family, Clostridiaceae family, Enterobacteriaceae family, Gardinella family, Pasteurellaceae family, Halobacteriaceae family, Helicobacter family, Legionallaceae family, Listeriaceae family are from a bacterial family selected from the group consisting of: Methylococcaceae family, Mycobacteriaceae, Neisseriaceae family, Oceanosspirillum family, Pasteurellaceae family, Streptococcaceae family, Pseudomonadaceae family, Rhizobiaceae family, Spirillum family, Spirosomaceae family, Staphylococcaceae family, Helicobacter family, Yersinia family, Bacillus antracis, and Vampirovibrio family; and(c) Tumor neoantigens or neoepitopes and tumor-associated antigens; tumor-associated antigens include artificial fusion proteins of HPV 16 E7 and E6 proteins, oncogenic viral antigens, cancer-testis antigens, carcinoembryonic antigens, tissue differentiation antigens, mutant protein antigens, adipophilin, AIM-2, ALDHIAI, BCLX(L), BING-4, CALCA, CD45, CPSF, cyclin DI, DKKI, ENAH (hMcna), Ga733 (EpCAM), EphA3, EZH2, FGF5, glypican-3, G250 / MN / CAIX, HER-2 / neu, IDOI, IGF2B3, IL13Rα2, intestinal carboxylesterase, α-fetoprotein, and kali. Krein 4, KIF20A, lengusin, M-CSF, MCSP, mdm-2, Meloe, MMP-2, MMP-7, MUCl, MUC5AC, p53 (non-mutant), PAX5, PBF, PRAME, PSMA, RAGE, RAGE-I, RGS5, RhoC, RNF43, RU2AS, cecernin 1, SOX10, STEAPI (prostate six-transmembrane epithelial antigen 1), survivin, telomerase, VEGF, WT1, EGF-R, CEA, CD20, CD33, CD52, MELANA / MART1, MART2, NY-ESO-1, p53, MAGE Al, MAGE A3, MAGE-4, MAGE-5, MAGE-6, CDK4, α-actinin-4, ARTC1, BCR-ABL, BCR-ABL fusion protein (b3a2), B-RAF, CASP-5, CASP-8, β-catenin, Cdc27, CDK4, CDKN2A, CLPP, COA-1, dek-can fusion protein, EFTUD2, elongation factor 2, ETV6-AML, ETV6-AML1 fusion protein, FLT3-ITD, FNl, GPNMB, LDLR-fucosyltransferase fusion protein, NFYC, OGT, OS-9, pml-RARα fusion protein, PRDX5, PTPRK, H-ras, K-ras (V-Ki-ras2) Kirsten rat sarcoma viral oncogene), N-ras, RBAF600, SIRT2, SNRPDl, SSX, SSX2, SYT-SSXl or -SSX2 fusion protein, TGF-βRII, triosephosphate isomerase, ormdm-2, LMP2, HPV E6, HPVE7, EGFRvIII (epidermal growth factor variant III), idiotype, GD2, ganglioside G2), Ras-mutant, p53 (mutant), proteinase 3 (PRI), tyrosinase, PSA, hTERT, sarcoma translocation breakpoint, EphA2, prostatic acid phosphatase (PAP), neo-PAP, ML-IAP, AFP, ERG (TMPRSS2 ETS fusion gene), NAI 7, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, TRP2, TRP2-Int2, GD3, fucosyl-GM1, mesothelin, PSCA, sLe(a), cyp1B1, PLACI, GM3, BORIS, Tn, globoH, NY-BR-I, SART3, STn, carbonic anhydrase IX, OY-TESI, sperm protein 17, LCK, high-molecular-weight melanoma-associated antigen (HMWMAA), AKAP-4, SSX2, XAGE 1, B7H3, legumain, Tie 2, Page 4, VEGFR2, MAD-CT-I, FAP, PDGFR-beta, MADCT-2, For-related antigen 1, TRPI, GP100, CA-125, CA19-9, calretinin, epithelial membrane antigen (EMA), epithelial tumor antigen (ETA), CD19, CD34, CD99, CDI 17, chromogranin, cytokeratin, desmin, glial fibrillary acidic protein (GFAP), macroscopic cystic disease fluid protein (GCDFP-15), HMB-45 antigen, Myo-D1, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase, synaptophysin, thyroglobulin, thyroid transcription factor-1, dimeric form of pyruvate kinase isoenzyme type M2 (tumor M2-PK), BAGE BAGE-1, CAGE, CTAGE, FATE, GAGE, GAGE-I, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, HCA661, HOM-TES-85, MAGEA, MAGEB, MAGEC, NA88, NY-SAR-35, SPANXBI, SPAI 7, SSX, SYCP1, TPTE, carbohydrate / ganglioside GM2 (carcinoembryonic antigen-immunogenicity-1 OFA-I-1), GM3, CA 15-3 (CA 27.29 / BCAA), CA 195, CA 242, CA 50, CAM43, CEA, EBNA, EF2, Epstein-Barr virus antigen, HLA-A2, HLA-Al 1, HSP70-2, KIAAO205, MUM-I, MUM-2, MUM-3, myosin class I, GnTV, Herv-K-mel, LAGE-I, LAGE-2, (sperm protein) SPI 7, SCP-I, P15(58), Hom / Mel-40, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, TSP-180, P185erbB2, p180erbB-3, c-met, nm-23H1, TAG-72, TAG-72-4, CA-72-4, CAM 17.1, NuMa, 13-catenin, p16, TAGE, CT7, 43-9F, 5T4, 791Tgp72, 13HCG, BCA225, BTAA, CD68 / KP1, CO-029, HTgp-175, M344, MG7-Ag, MOV18, NB / 70K, NYCO-1, RCAS1, SDCCAG16, TA-90, TAAL6, TLP, TPS, CD22, CD27, CD30, CD70, prostein, TARP (T cell receptor gamma alternative reading frame protein), Trp-p8, integrin avβ3 (CD61), galactin, or selected from the group consisting of Ral-B, CD123, CLL-1, CD38, CS-1, CD138, and ROR1.

[0030] In certain embodiments, expression of the heterologous non-arenavirus polypeptide or expression of the second heterologous non-arenavirus polypeptide is under the control of an arenavirus 3' UTR; and the expression level of the heterologous non-arenavirus polypeptide or the expression level of the second heterologous non-arenavirus polypeptide is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold higher than the expression level of the same heterologous non-arenavirus polypeptide expressed under the control of the respective arenavirus 5' UTR or the expression level of the same second heterologous non-arenavirus polypeptide expressed under the control of the respective arenavirus 5' UTR.

[0031] In certain embodiments, expression of a heterologous non-arenavirus polypeptide is under the control of an arenavirus 3' UTR and expression of a second heterologous non-arenavirus polypeptide is under the control of an arenavirus 5' UTR, wherein the proportion of cells expressing both the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide after infection of a population of cells with arenavirus particles containing genomes comprising nucleotide sequences encoding the same heterologous non-arenavirus polypeptide and the same second heterologous non-arenavirus polypeptide expressed under the control of the arenavirus 5' UTR. The heterologous non-arenavirus polypeptide is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold greater than the proportion of cells expressing both the same heterologous non-arenavirus polypeptide and the same second heterologous non-arenavirus polypeptide expressed under the control of an arenavirus 5' UTR after infection of a comparable population of cells with arenavirus particles containing a genome comprising a nucleotide sequence comprising the nucleotide sequence.

[0032] In certain embodiments, provided herein are translation products of the nucleotide sequences provided herein.

[0033] In some embodiments, provided herein is an arenavirus particle comprising a genome comprising a nucleotide sequence provided herein. In some embodiments, the genome of the arenavirus particle consists of an S segment and an L segment.

[0034] In some embodiments, the arenavirus particle is trisegmented. In some embodiments, the trisegmented arenavirus particle comprises two S segments and one L segment. In some embodiments, the trisegmented arenavirus particle comprises one S segment and two L segments.

[0035] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of an arenavirus 3'UTR, and encoding a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of an arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; consists of; and wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0036] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of the arenavirus 3'UTR, and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; consists of; and wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0037] In some embodiments, the arenavirus particle is derived from a Lassa virus. In some embodiments, the arenavirus particle is derived from a lymphocytic choriomeningitis virus (LCMV). In some embodiments, the LCMV is the MP strain, the WE strain, the Armstrong strain, or the Armstrong clone 13 strain. In some embodiments, the arenavirus particle is derived from a Piquinde virus (PICV). In some embodiments, the arenavirus particle is derived from Junin virus vaccine Candid #1 or Junin virus vaccine XJ clone 3 strain. In some embodiments, the arenavirus particle is derived from an Oliveros virus. In some embodiments, the arenavirus particle is derived from a Tamiami virus. In some embodiments, the arenavirus particle is derived from a Mobara virus. In some embodiments, the arenavirus particle is derived from a Mopeia virus. In some embodiments, the arenavirus particle is derived from a Yippee virus. In some embodiments, the arenavirus particle is derived from an Amapari virus. In some embodiments, the arenavirus particle is derived from a Flexar virus. In some embodiments, the arenavirus particle is derived from a Gunarito virus. In some embodiments, the arenavirus particle is derived from a Latinovirus. In some embodiments, the arenavirus particle is derived from a Machupovirus. In some embodiments, the arenavirus particle is derived from a Paranavirus. In some embodiments, the arenavirus particle is derived from a Piritarvirus. In some embodiments, the arenavirus particle is derived from a Sabiavirus. In some embodiments, the arenavirus particle is derived from a Tacaribevirus. In some embodiments, the arenavirus particle is derived from a Bear Canyonvirus. In some embodiments, the arenavirus particle is derived from a Whitewater Arroyovirus. In some embodiments, the arenavirus particle is derived from an Alpahuayovirus (ALLV). In some embodiments, the arenavirus particle is derived from an Alxavirus. In some embodiments, the arenavirus particle is derived from a Chaparevirus. In some embodiments, the arenavirus particle is derived from a Lijiangvirus.In certain embodiments, the arenavirus particle is derived from a Cupixivirus. In certain embodiments, the arenavirus particle is derived from a Gairovirus. In certain embodiments, the arenavirus particle is derived from a Loei River virus. In certain embodiments, the arenavirus particle is derived from a Lujo virus. In certain embodiments, the arenavirus particle is derived from a Lunavirus. In certain embodiments, the arenavirus particle is derived from a Lulivirus. In certain embodiments, the arenavirus particle is derived from a Runk virus. In certain embodiments, the arenavirus particle is derived from a Mariental virus. In certain embodiments, the arenavirus particle is derived from a Merinowalk virus. In certain embodiments, the arenavirus particle is derived from a Morogoro virus. In certain embodiments, the arenavirus particle is derived from an Okahandja virus. In certain embodiments, the arenavirus particle is derived from an Aporevirus. In certain embodiments, the arenavirus particle is derived from a Ryukyu virus. In certain embodiments, the arenavirus particle is derived from a Solwezi virus. In certain embodiments, the arenavirus particle is derived from a Thule virus. In certain embodiments, the arenavirus particle is derived from a Wenzhou virus. In some embodiments, the arenavirus particle is derived from a Big Brushy Tank virus. In some embodiments, the arenavirus particle is derived from a Catalinavirus. In some embodiments, the arenavirus particle is derived from a Skinner Tank virus. In some embodiments, the arenavirus particle is derived from a Tonto River virus. In some embodiments, the arenavirus particle is derived from a Shapley virus.

[0038] In certain embodiments, the genome of an arenavirus particle encodes a heterologous non-arenavirus polypeptide, and the growth or infectivity of the arenavirus particle is no less than that of a second arenavirus particle, wherein the genome of the second arenavirus particle encodes the same heterologous non-arenavirus polypeptide; and wherein all arenavirus GP, NP, Z, and L in the second arenavirus particle are each expressed as a single ORF.

[0039] In some embodiments, the arenavirus particles are infectious and replicable. In some embodiments, the arenavirus particles are attenuated compared to their parent virus. In some embodiments, the arenavirus particles are infectious but unable to produce further infectious progeny in non-complementing cells.

[0040] In certain embodiments, the titer of the arenavirus particles is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold lower than the titer of the respective wild-type parent arenavirus particles during persistent infection in AGRAG mice.

[0041] In certain embodiments, the arenavirus particle expresses a heterologous non-arenavirus polypeptide under the control of an arenavirus 3' UTR; and wherein the arenavirus particle induces at least about a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold greater immune response to the heterologous non-arenavirus polypeptide in a subject after the arenavirus particle is administered to the subject, compared to after another arenavirus particle expressing the same heterologous non-arenavirus polypeptide under the control of an arenavirus 5' UTR is administered to the subject or a comparable subject.

[0042] In certain embodiments, the nucleotide sequence is a DNA sequence that can be transcribed into an arenavirus genome or antigenome segment. In certain embodiments, provided herein are methods for producing arenavirus genome or antigenome RNA segments, comprising transcribing a DNA sequence provided herein.

[0043] In certain embodiments, provided herein is a method of generating arenavirus particles, comprising: a) transfecting a host cell with one or more of the DNA sequences provided herein or one or more RNA sequences each transcribed in vitro from the DNA sequences provided herein; b) transfecting said host cell with a nucleotide sequence encoding an arenavirus trans-acting factor; c) maintaining the host cells under conditions favorable for virus formation; and d) recovering the arenavirus particles. The method includes:

[0044] In some embodiments, the one or more DNA sequences are transcribed using a bidirectional promoter. a) RNA polymerase I promoter; b) an RNA polymerase II promoter; and c) T7 promoter The transcription is under the control of a promoter selected from the group consisting of:

[0045] In certain embodiments, provided herein is a DNA expression vector comprising a nucleotide sequence provided herein.

[0046] In certain embodiments, provided herein are methods of rescuing arenavirus particles using the nucleotide sequences provided herein.

[0047] In certain embodiments, provided herein is a host cell comprising a nucleotide sequence provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein.

[0048] In certain embodiments, provided herein is a vaccine comprising a nucleotide sequence provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0049] In certain embodiments, provided herein is a pharmaceutical composition comprising a nucleotide sequence provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0050] 3.2 Arenavirus Particles and Related Compositions and Methods In another aspect, provided herein are arenavirus particles. In certain embodiments, provided herein are arenavirus particles that have been modified so that the arenavirus ORFs are separated by two or more mRNA transcripts.

[0051] In certain embodiments, at least one of the mRNA transcripts comprises an internal ribosome entry site (IRES).

[0052] In certain embodiments, the mRNA transcript can be transcribed from an arenavirus genome or antigenome segment. In certain embodiments, the arenavirus genome or antigenome segment is an S segment. In certain embodiments, the arenavirus genome or antigenome segment is an L segment.

[0053] In certain embodiments, the two or more mRNA transcripts are under the control of the arenavirus 3'UTR or the arenavirus 5'UTR.

[0054] In certain embodiments, the arenavirus ORF is SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:1 02, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, the arenavirus ORF encodes a polypeptide comprising an amino acid sequence identical to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.

[0055] In one embodiment, the arenavirus ORF encodes an arenavirus GP signal peptide, arenavirus GP1 and GP2, and the arenavirus GP signal peptide or a functional fragment thereof is expressed from a first mRNA transcript (e.g., a viral mRNA transcript) and arenavirus GP1 and GP2 are expressed from a second mRNA transcript (e.g., a viral mRNA transcript).

[0056] In certain embodiments, the first mRNA transcript is under the control of an arenavirus 3'UTR.

[0057] In certain embodiments, the second mRNA transcript further encodes a heterologous non-arenavirus signal peptide.

[0058] In certain embodiments, the heterologous non-arenavirus signal peptide is the signal peptide of the vesicular stomatitis virus serotype Indiana glycoprotein.

[0059] In certain embodiments, the first mRNA transcript further comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide or arenavirus GP, NP, Z, and L.

[0060] In certain embodiments, the heterologous non-arenavirus polypeptide is an antigen derived from an infectious organism, a tumor, or an allergen. In certain embodiments, the antigen is selected from the group consisting of: (a) Viral antigens. The viral antigen is from a viral family selected from the group consisting of Adenoviridae, Herpesviridae, Leviviridae, Orthomyxoviridae, Parvoviridae, Filoviridae, Hantaviridae, Poxviridae, Papillomaviridae, Polyomaviridae, Paramyxoviridae, Pneumoviridae, Picornaviridae, Reoviridae, Retroviridae, Flaviviridae, Hepadnaviridae, Togaviridae, Rhabdoviridae, Arenaviridae, and Coronaviridae; (b) bacterial antigens, wherein the bacterial antigen is from a bacterial family selected from the group consisting of Aquaspirillaceae, Azospirillaceae, Azotobacteraceae, Bacteroidetaceae, Bartonellaceae, Bdellovibrioceae, Campylobacteraceae, Chlamydiaceae, Clostridiaceae, Enterobacteriaceae, Gardinellaceae, Pasteurellaceae, Halobacteriumceae, Helicobacteraceae, Legionellaceae, Listeriaceae, Methylococcusceae, Mycobacteriaceae, Neisseriaceae, Oceanospirillaceae, Pasteurellaceae, Streptococcusceae, Pseudomonadaceae, Rhizobiumceae, Spirillaceae, Spirosomaceae, Staphylococcusceae, Helicobacteraceae, Yersiniaceae, Bacillus anthracis, and Vampirovibrionaceae; and (c) Tumor neoantigens or neoepitopes and tumor-associated antigens; tumor-associated antigens include artificial fusion proteins of HPV 16 E7 and E6 proteins, oncogenic viral antigens, cancer-testis antigens, carcinoembryonic antigens, tissue differentiation antigens, mutant protein antigens, adipophilin, AIM-2, ALDHIAI, BCLX(L), BING-4, CALCA, CD45, CPSF, cyclin DI, DKKI, ENAH (hMcna), Ga733 (EpCAM), EphA3, EZH2, FGF5, glypican-3, G250 / MN / CAIX, HER-2 / neu, IDOI, IGF2B3, IL13Rα2, intestinal carboxylesterase, α-fetoprotein, and kali. Krein 4, KIF20A, lengusin, M-CSF, MCSP, mdm-2, Meloe, MMP-2, MMP-7, MUCl, MUC5AC, p53 (non-mutant), PAX5, PBF, PRAME, PSMA, RAGE, RAGE-I, RGS5, RhoC, RNF43, RU2AS, cecernin 1, SOX10, STEAPI (prostate six-transmembrane epithelial antigen 1), survivin, telomerase, VEGF, WT1, EGF-R, CEA, CD20, CD33, CD52, MELANA / MART1, MART2, NY-ESO-1, p53, MAGE Al, MAGE A3, MAGE-4, MAGE-5, MAGE-6, CDK4, α-actinin-4, ARTC1, BCR-ABL, BCR-ABL fusion protein (b3a2), B-RAF, CASP-5, CASP-8, β-catenin, Cdc27, CDK4, CDKN2A, CLPP, COA-1, dek-can fusion protein, EFTUD2, elongation factor 2, ETV6-AML, ETV6-AML1 fusion protein, FLT3-ITD, FNl, GPNMB, LDLR-fucosyltransferase fusion protein, NFYC, OGT, OS-9, pml-RARα fusion protein, PRDX5, PTPRK, H-ras, K-ras (V-Ki-ras2) Kirsten rat sarcoma viral oncogene), N-ras, RBAF600, SIRT2, SNRPDl, SSX, SSX2, SYT-SSXl or -SSX2 fusion protein, TGF-βRII, triosephosphate isomerase, ormdm-2, LMP2, HPV E6, HPVE7, EGFRvIII (epidermal growth factor variant III), idiotype, GD2, ganglioside G2), Ras-mutant, p53 (mutant), proteinase 3 (PRI), tyrosinase, PSA, hTERT, sarcoma translocation breakpoint, EphA2, prostatic acid phosphatase (PAP), neo-PAP, ML-IAP, AFP, ERG (TMPRSS2 ETS fusion gene), NAI 7, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, TRP2, TRP2-Int2, GD3, fucosyl-GM1, mesothelin, PSCA, sLe(a), cyp1B1, PLACI, GM3, BORIS, Tn, globoH, NY-BR-I, SART3, STn, carbonic anhydrase IX, OY-TESI, sperm protein 17, LCK, high-molecular-weight melanoma-associated antigen (HMWMAA), AKAP-4, SSX2, XAGE 1, B7H3, legumain, Tie 2, Page 4, VEGFR2, MAD-CT-I, FAP, PDGFR-beta, MADCT-2, For-related antigen 1, TRPI, GP100, CA-125, CA19-9, calretinin, epithelial membrane antigen (EMA), epithelial tumor antigen (ETA), CD19, CD34, CD99, CDI 17, chromogranin, cytokeratin, desmin, glial fibrillary acidic protein (GFAP), macroscopic cystic disease fluid protein (GCDFP-15), HMB-45 antigen, Myo-D1, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase, synaptophysin, thyroglobulin, thyroid transcription factor-1, dimeric form of pyruvate kinase isoenzyme type M2 (tumor M2-PK), BAGE BAGE-1, CAGE, CTAGE, FATE, GAGE, GAGE-I, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, HCA661, HOM-TES-85, MAGEA, MAGEB, MAGEC, NA88, NY-SAR-35, SPANXBI, SPAI 7, SSX, SYCP1, TPTE, carbohydrate / ganglioside GM2 (carcinoembryonic antigen-immunogenicity-1 OFA-I-1), GM3, CA 15-3 (CA 27.29 / BCAA), CA 195, CA 242, CA 50, CAM43, CEA, EBNA, EF2, Epstein-Barr virus antigen, HLA-A2, HLA-Al 1, HSP70-2, KIAAO205, MUM-I, MUM-2, MUM-3, myosin class I, GnTV, Herv-K-mel, LAGE-I, LAGE-2, (sperm protein) SPI 7, SCP-I, P15(58), Hom / Mel-40, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, TSP-180, P185erbB2, p180erbB-3, c-met, nm-23H1, TAG-72, TAG-72-4, CA-72-4, CAM 17.1, NuMa, 13-catenin, p16, TAGE, CT7, 43-9F, 5T4, 791Tgp72, 13HCG, BCA225, BTAA, CD68 / KP1, CO-029, HTgp-175, M344, MG7-Ag, MOV18, NB / 70K, NYCO-1, RCAS1, SDCCAG16, TA-90, TAAL6, TLP, TPS, CD22, CD27, CD30, CD70, prostein, TARP (T cell receptor gamma alternative reading frame protein), Trp-p8, integrin avβ3 (CD61), galactin, or selected from the group consisting of Ral-B, CD123, CLL-1, CD38, CS-1, CD138, and ROR1.

[0061] In certain embodiments, the expression level of a heterologous non-arenavirus polypeptide expressed under the control of an arenavirus 3'UTR is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold higher than the expression level of the same heterologous non-arenavirus polypeptide expressed under the control of the respective arenavirus 5'UTR.

[0062] In certain embodiments, expression of a first of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 3' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a second S segment, wherein the proportion of cells that express both of these two heterologous non-arenavirus polypeptides after infection of a population of cells with arenavirus particles is greater than the proportion of cells that express both of the same two heterologous non-arenavirus polypeptides after infection of an equivalent population of cells with arenavirus particles that express the same two heterologous non-arenavirus polypeptides under the control of arenavirus 5' UTRs. and wherein expression of a first of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a second S segment.

[0063] In certain embodiments, the genome of an arenavirus particle encodes a heterologous non-arenavirus polypeptide and / or a second heterologous non-arenavirus polypeptide, and the growth or infectivity of the arenavirus particle is no less than that of a second arenavirus particle, wherein the genome of the second arenavirus particle encodes the same heterologous non-arenavirus polypeptide and / or the same second heterologous non-arenavirus polypeptide; and wherein all arenavirus GP, NP, Z, and L in the second arenavirus particle are each expressed as a single ORF.

[0064] In certain embodiments, the genome of the arenavirus particle consists of an S segment and an L segment.

[0065] In some embodiments, the arenavirus particle is trisegmented. In some embodiments, the trisegmented arenavirus particle comprises two S segments and one L segment. In some embodiments, the trisegmented arenavirus particle comprises one S segment and two L segments.

[0066] In certain embodiments, the arenavirus particle comprises the genome organization outlined in Figure 4C. In certain embodiments, the arenavirus particle comprises the genome organization outlined in Figure 4E.

[0067] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of an arenavirus 3'UTR, and encoding a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of an arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; consists of; and wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0068] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of the arenavirus 3'UTR, and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; Consists of; wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0069] In some embodiments, the arenavirus particle is derived from a Lassa virus. In some embodiments, the arenavirus particle is derived from a lymphocytic choriomeningitis virus (LCMV). In some embodiments, the LCMV is the MP strain, the WE strain, the Armstrong strain, or the Armstrong clone 13 strain. In some embodiments, the arenavirus particle is derived from a Piquinde virus (PICV). In some embodiments, the arenavirus particle is derived from a Junin virus vaccine, Candid #1, or a Junin virus vaccine, XJ clone 3 strain. In some embodiments, the arenavirus particle is derived from an Oliveros virus. In some embodiments, the arenavirus particle is derived from a Tamiami virus. In some embodiments, the arenavirus particle is derived from a Mobara virus. In some embodiments, the arenavirus particle is derived from a Mopeia virus. In some embodiments, the arenavirus particle is derived from a Yippee virus. In some embodiments, the arenavirus particle is derived from an Amapari virus. In some embodiments, the arenavirus particle is derived from a Flexar virus. In some embodiments, the arenavirus particle is derived from a Gunarito virus. In some embodiments, the arenavirus particle is derived from a Latinovirus. In some embodiments, the arenavirus particle is derived from a Machupovirus. In some embodiments, the arenavirus particle is derived from a Paranavirus. In some embodiments, the arenavirus particle is derived from a Piritarvirus. In some embodiments, the arenavirus particle is derived from a Sabiavirus. In some embodiments, the arenavirus particle is derived from a Tacaribevirus. In some embodiments, the arenavirus particle is derived from a Bear Canyonvirus. In some embodiments, the arenavirus particle is derived from a Whitewater Arroyovirus. In some embodiments, the arenavirus particle is derived from an Alpahuayovirus (ALLV). In some embodiments, the arenavirus particle is derived from an Alxavirus. In some embodiments, the arenavirus particle is derived from a Chaparevirus. In some embodiments, the arenavirus particle is derived from a Lijiangvirus.In certain embodiments, the arenavirus particle is derived from a Cupixivirus. In certain embodiments, the arenavirus particle is derived from a Gairovirus. In certain embodiments, the arenavirus particle is derived from a Loei River virus. In certain embodiments, the arenavirus particle is derived from a Lujo virus. In certain embodiments, the arenavirus particle is derived from a Lunavirus. In certain embodiments, the arenavirus particle is derived from a Lulivirus. In certain embodiments, the arenavirus particle is derived from a Runk virus. In certain embodiments, the arenavirus particle is derived from a Mariental virus. In certain embodiments, the arenavirus particle is derived from a Merinowalk virus. In certain embodiments, the arenavirus particle is derived from a Morogoro virus. In certain embodiments, the arenavirus particle is derived from an Okahandja virus. In certain embodiments, the arenavirus particle is derived from an Aporevirus. In certain embodiments, the arenavirus particle is derived from a Ryukyu virus. In certain embodiments, the arenavirus particle is derived from a Solwezi virus. In certain embodiments, the arenavirus particle is derived from a Thule virus. In certain embodiments, the arenavirus particle is derived from a Wenzhou virus. In some embodiments, the arenavirus particle is derived from a Big Brushy Tank virus. In some embodiments, the arenavirus particle is derived from a Catalinavirus. In some embodiments, the arenavirus particle is derived from a Skinner Tank virus. In some embodiments, the arenavirus particle is derived from a Tonto River virus. In some embodiments, the arenavirus particle is derived from a Shapley virus.

[0070] In some embodiments, the arenavirus particles are infectious and replicable. In some embodiments, the arenavirus particles are attenuated compared to their parent wild-type virus. In some embodiments, the arenavirus particles are infectious but unable to produce further infectious progeny in non-complementing cells.

[0071] In certain embodiments, the titer of the arenavirus particles is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold lower than the titer of the respective wild-type parent arenavirus particles during persistent infection in AGRAG mice.

[0072] In certain embodiments, the arenavirus particle expresses a heterologous non-arenavirus polypeptide under the control of an arenavirus 3' UTR; and wherein the arenavirus particle induces at least about a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold greater immune response to the heterologous non-arenavirus polypeptide in a subject after the arenavirus particle is administered to the subject, compared to after another arenavirus particle expressing the same heterologous non-arenavirus polypeptide under the control of an arenavirus 5' UTR is administered to the subject or a comparable subject.

[0073] In certain embodiments, provided herein are translation products of mRNA transcripts of the genomes of the arenavirus particles provided herein.

[0074] In certain embodiments, provided herein is a cDNA of an mRNA transcript of the genome of an arenavirus particle provided herein, wherein the cDNA can be transcribed into an arenavirus genome or antigenome segment.

[0075] In certain embodiments, provided herein are methods for producing arenavirus genome or antigenome segments, comprising transcribing a cDNA provided herein.

[0076] In certain embodiments, provided herein is a method of generating arenavirus particles, comprising: a) transfecting a host cell with one or more cDNAs of mRNA transcripts of the genomes of arenavirus particles provided herein or one or more RNA sequences each transcribed in vitro from a cDNA of an mRNA transcript of the genome of an arenavirus particle provided herein; b) transfecting said host cell with a nucleotide sequence encoding an arenavirus trans-acting factor; c) maintaining the host cells under conditions favorable for virus formation; and d) recovering the arenavirus particles. :A method including:

[0077] In some embodiments, the one or more cDNA sequences are transcribed using a bidirectional promoter. a) RNA polymerase I promoter; b) an RNA polymerase II promoter; and c) T7 promoter The transcription is under the control of a promoter selected from the group consisting of:

[0078] In certain embodiments, provided herein are DNA expression vectors comprising a DNA sequence encoding an mRNA transcript of the genome of an arenavirus particle provided herein.

[0079] In certain embodiments, provided herein are methods of rescuing arenavirus particles using mRNA transcripts of the genomes of arenavirus particles provided herein or their cDNA sequences.

[0080] In certain embodiments, provided herein is a host cell comprising an arenavirus particle provided herein, a translation product provided herein, a cDNA provided herein, or a DNA expression vector provided herein.

[0081] In certain embodiments, provided herein is a vaccine comprising an arenavirus particle provided herein, a translation product provided herein, a cDNA provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0082] In certain embodiments, provided herein is a pharmaceutical composition comprising an arenavirus particle provided herein, a translation product provided herein, a cDNA provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0083] 3.3 Arenavirus Genome or Antigenome Segments and Related Compositions and Methods In another aspect, provided herein is an arenavirus genome or antigenome segment. In one embodiment, provided herein is an arenavirus genome or antigenome segment that has been modified such that viral transcription produces a first mRNA transcript and a second mRNA transcript, wherein said first mRNA transcript comprises a nucleotide sequence encoding a functional fragment of a first polypeptide, and said first mRNA transcript does not encode the full-length first polypeptide; wherein the second mRNA transcript is a) a second polypeptide; or b) a functional fragment of the first polypeptide, and the second mRNA transcript does not encode the full-length first polypeptide; or c) a functional fragment of the second polypeptide, and the second mRNA transcript does not encode the full-length second polypeptide; or d) Heterologous Non-Arenavirus Polypeptides and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenavirus GP, NP, Z, and L.

[0084] In certain embodiments, the first mRNA transcript further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide, wherein said third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein said heterologous non-arenavirus polypeptide and said second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0085] In certain embodiments, the second mRNA transcript further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide, wherein said third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein said heterologous non-arenavirus polypeptide and said second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0086] In certain embodiments, the arenaviruses GP, NP, Z, and L are derived from LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0087] In one embodiment, provided herein is a method for detecting a viral transcription factor (VTR) in a mammalian cell, the method comprising: a) a functional fragment of a first polypeptide, and b) a heterologous non-arenavirus polypeptide or a second polypeptide an arenavirus genome or antigenome segment modified to produce an mRNA transcript encoding: wherein the mRNA transcript does not encode a full-length first polypeptide; and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenavirus GP, NP, Z, and L.

[0088] In certain embodiments, the mRNA transcript is a first mRNA transcript, and viral transcription of an arenavirus genome or antigenome segment further produces a second mRNA transcript; wherein the second mRNA transcript comprises a nucleotide sequence encoding a third polypeptide; a functional fragment of a third polypeptide; or a second heterologous non-arenavirus polypeptide; wherein the third polypeptide is different from the first and second polypeptides and is selected from the group consisting of arenavirus GP, NP, Z, and L, and wherein the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide are the same as or different from one another.

[0089] In certain embodiments, the second mRNA transcript comprises a nucleotide sequence encoding a functional fragment of the first polypeptide, wherein the functional fragment encoded by the first mRNA transcript differs from the functional fragment encoded by the second mRNA transcript.

[0090] In certain embodiments, viral transcription of the arenavirus genome or antigenome segment does not further give rise to a second mRNA transcript.

[0091] In certain embodiments, the mRNA transcript comprises an internal ribosome entry site (IRES).

[0092] In certain embodiments, the arenavirus genome or antigenome segment is an S segment. In certain embodiments, the arenavirus genome or antigenome segment is an L segment.

[0093] In certain embodiments, the functional fragment is under the control of an arenavirus 3'UTR. In certain embodiments, the functional fragment is under the control of an arenavirus 5'UTR.

[0094] In certain embodiments, the first, second, and third polypeptides are each selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, or SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, and / or 100% identical to the amino acid sequence of SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.

[0095] In certain embodiments, the first polypeptide comprises an amino acid sequence identical to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.

[0096] In some embodiments, the functional fragment of the first polypeptide is selected from the group consisting of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, SEQ ID NO: and / or SEQ ID NO:135, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, SEQ ID NO:136, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.

[0097] In certain embodiments, the functional fragment is an arenavirus GP signal peptide or a functional fragment thereof.

[0098] In certain embodiments, the heterologous non-arenavirus polypeptide, the second heterologous non-arenavirus polypeptide, or both heterologous non-arenavirus polypeptides are each an antigen derived from an infectious organism, a tumor, or an allergen. In certain embodiments, the antigen is selected from the group consisting of: (a) a viral antigen, wherein the viral antigen is from a viral family selected from the group consisting of Adenoviridae, Herpesviridae, Leviviridae, Orthomyxoviridae, Parvoviridae, Filoviridae, Hantaviridae, Poxviridae, Papillomaviridae, Polyomaviridae, Paramyxoviridae, Pneumoviridae, Picornaviridae, Reoviridae, Retroviridae, Flaviviridae, Hepadnaviridae, Togaviridae, Rhabdoviridae, Arenaviridae, and Coronaviridae; (b) a bacterial antigen, wherein the bacterial antigen is from a bacterial family selected from the group consisting of Aquaspirillaceae, Azospirillaceae, Azotobacteraceae, Bacteroidetaceae, Bartonellaceae, Bdellovibrioceae, Campylobacteraceae, Chlamydiaceae, Clostridiaceae, Enterobacteriaceae, Gardinellaceae, Pasteurellaceae, Halobacteraceae, Helicobacteraceae, Legionellaceae, Listeriaceae, Methylococcusceae, Mycobacteriaceae, Neisseriaceae, Oceanospirillaceae, Pasteurellaceae, Streptococciaceae, Pseudomonadaceae, Rhizobiumceae, Spirillaceae, Spirosomaceae, Staphylococciaceae, Helicobacteraceae, Yersinaceae, Bacillus anthracis, and Vampirovibrionaceae; and (c) Tumor neoantigens or neoepitopes and tumor-associated antigens; tumor antigens include artificial fusion proteins of HPV 16 E7 and E6 proteins, oncogenic viral antigens, cancer-testis antigens, carcinoembryonic antigens, tissue differentiation antigens, mutant protein antigens, adipophilin, AIM-2, ALDHIAI, BCLX(L), BING-4, CALCA, CD45, CPSF, cyclin DI, DKKI, ENAH (hMcna), Ga733 (EpCAM), EphA3, EZH2, FGF5, glypican-3, G250 / MN / CAIX, HER-2 / neu, IDOI, IGF2B3, IL13Rα2, intestinal carboxylesterase, α-fetoprotein, and kali. Krein 4, KIF20A, lengusin, M-CSF, MCSP, mdm-2, Meloe, MMP-2, MMP-7, MUCl, MUC5AC, p53 (non-mutant), PAX5, PBF, PRAME, PSMA, RAGE, RAGE-I, RGS5, RhoC, RNF43, RU2AS, cecernin 1, SOX10, STEAPI (prostate six-transmembrane epithelial antigen 1), survivin, telomerase, VEGF, WT1, EGF-R, CEA, CD20, CD33, CD52, MELANA / MART1, MART2, NY-ESO-1, p53, MAGE Al, MAGE A3, MAGE-4, MAGE-5, MAGE-6, CDK4, α-actinin-4, ARTC1, BCR-ABL, BCR-ABL fusion protein (b3a2), B-RAF, CASP-5, CASP-8, β-catenin, Cdc27, CDK4, CDKN2A, CLPP, COA-1, dek-can fusion protein, EFTUD2, elongation factor 2, ETV6-AML, ETV6-AML1 fusion protein, FLT3-ITD, FNl, GPNMB, LDLR-fucosyltransferase fusion protein, NFYC, OGT, OS-9, pml-RARα fusion protein, PRDX5, PTPRK, H-ras, K-ras (V-Ki-ras2) Kirsten rat sarcoma viral oncogene), N-ras, RBAF600, SIRT2, SNRPDl, SSX, SSX2, SYT-SSXl or -SSX2 fusion protein, TGF-βRII, triosephosphate isomerase, ormdm-2, LMP2, HPV E6, HPVE7, EGFRvIII (epidermal growth factor variant III), idiotype, GD2, ganglioside G2), Ras-mutant, p53 (mutant), proteinase 3 (PRI), tyrosinase, PSA, hTERT, sarcoma translocation breakpoint, EphA2, prostatic acid phosphatase (PAP), neo-PAP, ML-IAP, AFP, ERG (TMPRSS2 ETS fusion gene), NAI 7, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, TRP2, TRP2-Int2, GD3, fucosyl-GM1, mesothelin, PSCA, sLe(a), cyp1B1, PLACI, GM3, BORIS, Tn, globoH, NY-BR-I, SART3, STn, carbonic anhydrase IX, OY-TESI, sperm protein 17, LCK, high-molecular-weight melanoma-associated antigen (HMWMAA), AKAP-4, SSX2, XAGE 1, B7H3, legumain, Tie 2, Page 4, VEGFR2, MAD-CT-I, FAP, PDGFR-beta, MADCT-2, For-related antigen 1, TRPI, GP100, CA-125, CA19-9, calretinin, epithelial membrane antigen (EMA), epithelial tumor antigen (ETA), CD19, CD34, CD99, CDI 17, chromogranin, cytokeratin, desmin, glial fibrillary acidic protein (GFAP), macroscopic cystic disease fluid protein (GCDFP-15), HMB-45 antigen, Myo-D1, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase, synaptophysin, thyroglobulin, thyroid transcription factor-1, dimeric form of pyruvate kinase isoenzyme type M2 (tumor M2-PK), BAGE BAGE-1, CAGE, CTAGE, FATE, GAGE, GAGE-I, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, HCA661, HOM-TES-85, MAGEA, MAGEB, MAGEC, NA88, NY-SAR-35, SPANXBI, SPAI 7, SSX, SYCP1, TPTE, carbohydrate / ganglioside GM2 (carcinoembryonic antigen-immunogenicity-1 OFA-I-1), GM3, CA 15-3 (CA 27.29 / BCAA), CA 195, CA 242, CA 50, CAM43, CEA, EBNA, EF2, Epstein-Barr virus antigen, HLA-A2, HLA-Al 1, HSP70-2, KIAAO205, MUM-I, MUM-2, MUM-3, myosin class I, GnTV, Herv-K-mel, LAGE-I, LAGE-2, (sperm protein) SPI 7, SCP-I, P15(58), Hom / Mel-40, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, TSP-180, P185erbB2, p180erbB-3, c-met, nm-23H1, TAG-72, TAG-72-4, CA-72-4, CAM 17.1, NuMa, 13-catenin, p16, TAGE, CT7, 43-9F, 5T4, 791Tgp72, 13HCG, BCA225, BTAA, CD68 / KP1, CO-029, HTgp-175, M344, MG7-Ag, MOV18, NB / 70K, NYCO-1, RCAS1, SDCCAG16, TA-90, TAAL6, TLP, TPS, CD22, CD27, CD30, CD70, prostein, TARP (T cell receptor gamma alternative reading frame protein), Trp-p8, integrin avβ3 (CD61), galactin, or selected from the group consisting of Ral-B, CD123, CLL-1, CD38, CS-1, CD138, and ROR1.

[0099] In certain embodiments, the first mRNA transcript comprises a nucleotide sequence encoding an arenavirus GP signal peptide, either alone or fused to a heterologous non-arenavirus polypeptide. In certain embodiments, the second mRNA transcript comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the first mRNA transcript is under the control of the arenavirus 3' UTR and the second mRNA transcript is under the control of the arenavirus 5' UTR.

[0100] In certain embodiments, the first mRNA transcript comprises a nucleotide sequence encoding an arenavirus GP signal peptide, either alone or fused to a heterologous non-arenavirus polypeptide. In certain embodiments, the second mRNA transcript comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide; wherein the heterologous non-arenavirus polypeptide encoded by the first mRNA transcript and the heterologous non-arenavirus polypeptide encoded by the second mRNA transcript are the same as or different from each other. In certain embodiments, the first mRNA transcript is under the control of an arenavirus 3' UTR and the second mRNA transcript is under the control of an arenavirus 5' UTR.

[0101] In certain embodiments, the first mRNA transcript comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the second mRNA transcript comprises a nucleotide sequence encoding NP. In certain embodiments, the first mRNA transcript is under the control of an arenavirus 5' UTR and the second mRNA transcript is under the control of an arenavirus 3' UTR.

[0102] In certain embodiments, the expression level of a heterologous non-arenavirus polypeptide expressed under the control of an arenavirus 3' UTR or the expression level of a second heterologous non-arenavirus polypeptide expressed under the control of an arenavirus 3' UTR is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, or 4-fold greater than the expression level of the same heterologous non-arenavirus polypeptide expressed under the control of the respective arenavirus 5' UTR. , 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold higher, or at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold higher than the expression level of the same second heterologous non-arenavirus polypeptide expressed under the control of the respective arenavirus 5' UTR.

[0103] In certain embodiments, expression of a first of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 3' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a second S segment, wherein the proportion of cells that express both of these two heterologous non-arenavirus polypeptides after infection of a population of cells with arenavirus particles is greater than the proportion of cells that express both of the same two heterologous non-arenavirus polypeptides after infection of an equivalent population of cells with arenavirus particles that express the same two heterologous non-arenavirus polypeptides under the control of arenavirus 5' UTRs. and wherein expression of a first of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a second S segment.

[0104] In certain embodiments, provided herein are translation products of the arenavirus genome or antigenome segments provided herein.

[0105] In certain embodiments, provided herein are arenavirus particles comprising an arenavirus genome or antigenome segment provided herein.

[0106] In certain embodiments, the genome of the arenavirus particle consists of an S segment and an L segment.

[0107] In some embodiments, the arenavirus particle is trisegmented. In some embodiments, the trisegmented arenavirus particle comprises two S segments and one L segment. In some embodiments, the trisegmented arenavirus particle comprises one S segment and two L segments.

[0108] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of an arenavirus 3'UTR, and encoding a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of an arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; consists of; and wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0109] In one embodiment, the genome of the arenavirus particle comprises: a) an S segment encoding an arenavirus GP signal peptide and a heterologous non-arenavirus polypeptide or only an arenavirus GP signal peptide under the control of the arenavirus 3'UTR, and encoding another heterologous non-arenavirus polypeptide or no polypeptide under the control of the arenavirus 5'UTR; b) an S segment encoding NP under the control of the arenavirus 3'UTR and a heterologous non-arenavirus signal peptide, arenavirus GP1, and arenavirus GP2 under the control of the arenavirus 5'UTR; and c) an L segment encoding an L protein under the control of the arenavirus 3'UTR and an L segment encoding a Z protein under the control of the arenavirus 5'UTR; Consists of; wherein the two heterologous non-arenavirus polypeptides are the same or different from each other.

[0110] In some embodiments, the arenavirus particle is derived from a Lassa virus. In some embodiments, the arenavirus particle is derived from a lymphocytic choriomeningitis virus (LCMV). In some embodiments, the LCMV is the MP strain, the WE strain, the Armstrong strain, or the Armstrong clone 13 strain. In some embodiments, the arenavirus particle is derived from a Piquinde virus (PICV). In some embodiments, the arenavirus particle is derived from a Junin virus vaccine, Candid #1, or a Junin virus vaccine, XJ clone 3 strain. In some embodiments, the arenavirus particle is derived from an Oliveros virus. In some embodiments, the arenavirus particle is derived from a Tamiami virus. In some embodiments, the arenavirus particle is derived from a Mobara virus. In some embodiments, the arenavirus particle is derived from a Mopeia virus. In some embodiments, the arenavirus particle is derived from a Yippee virus. In some embodiments, the arenavirus particle is derived from an Amapari virus. In some embodiments, the arenavirus particle is derived from a Flexar virus. In some embodiments, the arenavirus particle is derived from a Gunarito virus. In some embodiments, the arenavirus particle is derived from a Latinovirus. In some embodiments, the arenavirus particle is derived from a Machupovirus. In some embodiments, the arenavirus particle is derived from a Paranavirus. In some embodiments, the arenavirus particle is derived from a Piritarvirus. In some embodiments, the arenavirus particle is derived from a Sabiavirus. In some embodiments, the arenavirus particle is derived from a Tacaribevirus. In some embodiments, the arenavirus particle is derived from a Bear Canyonvirus. In some embodiments, the arenavirus particle is derived from a Whitewater Arroyovirus. In some embodiments, the arenavirus particle is derived from an Alpahuayovirus (ALLV). In some embodiments, the arenavirus particle is derived from an Alxavirus. In some embodiments, the arenavirus particle is derived from a Chaparevirus. In some embodiments, the arenavirus particle is derived from a Lijiangvirus.In certain embodiments, the arenavirus particle is derived from a Cupixivirus. In certain embodiments, the arenavirus particle is derived from a Gairovirus. In certain embodiments, the arenavirus particle is derived from a Loei River virus. In certain embodiments, the arenavirus particle is derived from a Lujo virus. In certain embodiments, the arenavirus particle is derived from a Lunavirus. In certain embodiments, the arenavirus particle is derived from a Lulivirus. In certain embodiments, the arenavirus particle is derived from a Runk virus. In certain embodiments, the arenavirus particle is derived from a Mariental virus. In certain embodiments, the arenavirus particle is derived from a Merinowalk virus. In certain embodiments, the arenavirus particle is derived from a Morogoro virus. In certain embodiments, the arenavirus particle is derived from an Okahandja virus. In certain embodiments, the arenavirus particle is derived from an Aporevirus. In certain embodiments, the arenavirus particle is derived from a Ryukyu virus. In certain embodiments, the arenavirus particle is derived from a Solwezi virus. In certain embodiments, the arenavirus particle is derived from a Thule virus. In certain embodiments, the arenavirus particle is derived from a Wenzhou virus. In some embodiments, the arenavirus particle is derived from a Big Brushy Tank virus. In some embodiments, the arenavirus particle is derived from a Catalinavirus. In some embodiments, the arenavirus particle is derived from a Skinner Tank virus. In some embodiments, the arenavirus particle is derived from a Tonto River virus. In some embodiments, the arenavirus particle is derived from a Shapley virus.

[0111] In certain embodiments, the genome of an arenavirus particle encodes a heterologous non-arenavirus polypeptide and / or a second heterologous non-arenavirus polypeptide, and the growth or infectivity of the arenavirus particle is no less than that of a second arenavirus particle, wherein the genome of the second arenavirus particle encodes the same heterologous non-arenavirus polypeptide and / or the same second heterologous non-arenavirus polypeptide; and wherein all arenavirus GP, NP, Z, and L in the second arenavirus particle are each expressed as a single ORF.

[0112] In some embodiments, the arenavirus particles are infectious and replicable. In some embodiments, the arenavirus particles are attenuated compared to their parent wild-type virus. In some embodiments, the arenavirus particles are infectious but unable to produce further infectious progeny in non-complementing cells.

[0113] In certain embodiments, the titer of the arenavirus particles is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold lower than the titer of the respective wild-type parent arenavirus particles during persistent infection in AGRAG mice.

[0114] In certain embodiments, the arenavirus particle expresses a heterologous non-arenavirus polypeptide under the control of an arenavirus 3' UTR; and wherein the arenavirus particle induces at least about a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 15-fold, 18-fold, 20-fold, 25-fold, or 30-fold greater immune response to the heterologous non-arenavirus polypeptide in a subject after the arenavirus particle is administered to the subject, compared to after another arenavirus particle expressing the same heterologous non-arenavirus polypeptide under the control of an arenavirus 5' UTR is administered to the subject or a comparable subject.

[0115] In certain embodiments, the arenavirus particles express two heterologous non-arenavirus polypeptides, wherein expression of a first of the two heterologous non-arenavirus polypeptides is under control of an arenavirus 3' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under control of an arenavirus 5' UTR in a second S segment, and wherein the proportion of cells that express both of these two heterologous non-arenavirus polypeptides after infection of a population of cells with the arenavirus particles is the same 2' UTR as the proportion of cells that express both of the two heterologous non-arenavirus polypeptides after infection of an equivalent population of cells with arenavirus particles expressing the same two heterologous non-arenavirus polypeptides under control of the arenavirus 5' UTR. and wherein expression of a first of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a first S segment and expression of a second of the two heterologous non-arenavirus polypeptides is under the control of an arenavirus 5' UTR in a second S segment.

[0116] In certain embodiments, provided herein are cDNAs of the arenavirus genome or antigenome segments provided herein.

[0117] In certain embodiments, provided herein are methods for producing arenavirus genome or antigenome segments, comprising transcribing a cDNA provided herein.

[0118] In certain embodiments, provided herein is a method of generating arenavirus particles, comprising: a) transfecting a host cell with one or more cDNA sequences of the arenavirus genome or antigenome segments provided herein or one or more RNA sequences transcribed in vitro from the cDNA sequences of the arenavirus genome or antigenome segments provided herein; b) transfecting said host cell with a nucleotide sequence encoding an arenavirus trans-acting factor; c) maintaining the host cells under conditions favorable for virus formation; and d) recovering the arenavirus particles. :A method including:

[0119] In some embodiments, the one or more cDNA sequences are transcribed using a bidirectional promoter. a) RNA polymerase I promoter; b) an RNA polymerase II promoter; and c) T7 promoter The transcription is under the control of a promoter selected from the group consisting of:

[0120] In certain embodiments, provided herein are DNA expression vectors comprising a DNA sequence encoding an arenavirus genome or antigenome segment provided herein.

[0121] In certain embodiments, provided herein are methods of rescuing arenavirus particles using arenavirus genome or antigenome segments provided herein or DNA sequences encoding arenavirus genome or antigenome segments.

[0122] In certain embodiments, provided herein is a host cell comprising an arenavirus genome or antigenome segment provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein.

[0123] In certain embodiments, provided herein is a vaccine comprising an arenavirus genome or antigenome segment provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0124] In certain embodiments, provided herein is a pharmaceutical composition comprising an arenavirus genome or antigenome segment provided herein, a translation product provided herein, an arenavirus particle provided herein, or a DNA expression vector provided herein, and a pharmaceutically acceptable carrier.

[0125] (3.4 Definition) As used herein, and unless otherwise indicated, the term "GP" refers to both arenavirus glycoproteins and any arenavirus glycoprotein precursors. In exemplary embodiments, arenavirus glycoprotein precursors can be post-translationally cleaved into a signal peptide, GP1, and GP2. In certain embodiments, arenavirus glycoproteins or any arenavirus glycoprotein precursors can be wild-type. In other embodiments, arenavirus glycoproteins or any arenavirus glycoprotein precursors can be recombinant. GPs are further described in Section 5.1.

[0126] As used herein, and unless otherwise indicated, the term "NP" refers to both arenavirus nucleoprotein and any arenavirus nucleoprotein precursor. In certain embodiments, the arenavirus nucleoprotein or any arenavirus nucleoprotein precursor may be wild-type. In other embodiments, the arenavirus nucleoprotein or any arenavirus nucleoprotein precursor may be recombinant. NP is further described in Section 5.1.

[0127] As used herein, and unless otherwise indicated, the term "Z" refers to both the arenavirus Z protein and any arenavirus Z protein precursor. In certain embodiments, the arenavirus Z protein or any arenavirus Z protein precursor may be wild-type. In other embodiments, the arenavirus Z protein or any arenavirus Z protein precursor may be recombinant. Z is further described in Section 5.1.

[0128] As used herein, and unless otherwise indicated, the term "L" refers to both an arenavirus L protein and any arenavirus L protein precursor. In certain embodiments, the arenavirus L protein or any arenavirus L protein precursor may be wild-type. In other embodiments, the arenavirus L protein or any arenavirus L protein precursor may be recombinant. L is further described in Section 5.1.

[0129] As used herein, and unless otherwise indicated, the term "functional fragment" refers to a fragment of a polypeptide. Functional fragments of the polypeptides described herein are not full-length polypeptides. In certain embodiments, the functional fragment may retain one or more functions known to those of skill in the art. In certain embodiments, the functional fragment may retain the biological function of the polypeptide from which it is derived. In an exemplary embodiment, the functional fragment may be a signal peptide that retains the function of mediating insertion of a glycoprotein precursor into the endoplasmic reticulum (ER) membrane. In further embodiments, in addition to the function of mediating insertion of a glycoprotein precursor into the ER membrane, the signal peptide may retain other functions, such as mediating cleavage of the polypeptide and / or acting as a trans-acting maturation factor. In other embodiments, the functional fragment may not retain any functions known to those of skill in the art. Functional fragments are further described in Section 5.2.

[0130] As used herein, and unless otherwise indicated, the term "heterologous non-arenavirus polypeptide" means a polypeptide that is not of arenavirus origin. In certain embodiments, the heterologous non-arenavirus polypeptide is a reporter protein (see Section 5.3.1). In other embodiments, the heterologous non-arenavirus polypeptide is a signal peptide (see Section 5.3.2), and in other embodiments, the heterologous non-arenavirus polypeptide is an antigen (see Section 5.3.3). 3.5 Conventions and Abbreviations [Table 1] TIFF0007783631000002.tif246170TIFF0007783631000003.tif152170 [Brief explanation of the drawings]

[0131] (4. Brief description of the drawings) [Figure 1]Figures 1A-1G: Published three-segmented arenavirus vector genome design strategies and the molecular mechanisms underlying r3LCMV phenotypic reversion and artLCMV genetic stability. Figures 1A-1E show schematic diagrams of the RNA segments forming the genomes of wild-type LCMV (Figure 1A), r3LCMV (Figure 1B), artLCMV (Figure 1C), r3LCMVrev (Figure 1D), and artLCMVrev (Figure 1E). Segment names are boxed and bolded. UTR: untranslated region; IGR: intergenic region; ORFs are indicated by arrows. GPC: full-length glycoprotein ORF (including native signal peptide); NP: nucleoprotein; L: RNA-dependent RNA polymerase L; Z: matrix protein; hp: heterologous non-arenavirus polypeptide. Figure 1F shows a nonhomologous intersegmental RNA recombination event that recombines the NP and GPC on a single RNA segment (Kallert SM et al. (2017) Nat Commun 8, 15327). This process underlies the spontaneous reversion of r3LCMV to a bisegmented viral genome with wild-type-like virulence. Figure 1G shows a hypothetical recombination event in artLCMV that recombines the GPC and NP on a single RNA segment that lacks the 5'UTR and therefore a functional viral promoter (Kallert SM et al. (2017) Nat Commun 8, 15327).

[0132] [Figure 2] Figure 2: Characteristics of published three-segmented arenavirus vector genome design strategies. Comparison of r3LCMV and r3LCMVrev for cell culture growth, genetic stability, and transgene expression levels from their SGP segments. Superscript numbers refer to the published basis for the rating. Genetic stability has not been tested for all vector design strategies ("Not tested").

[0133] [Figure 3]Figures 3A-3B: Domain structure of arenavirus glycoproteins and strategies for separating the signal peptide from the GP1 and GP2 domains in the viral transcription unit. Figure 3A shows a schematic diagram of the arenavirus glycoprotein (GPC), which is composed of a signal peptide (SP), a GP1 domain (an external globular receptor-binding domain on the virion glycoprotein complex), and a GP2 transmembrane stalk domain. While signal peptidase cleaves the signal peptide concomitantly with polypeptide synthesis, SKI-1 / S1P ("S1P") cleaves between GP1 and GP2 after translation, rendering the glycoprotein complex biologically active. Figure 3B shows the separation of the arenavirus GP signal peptide (SP) into one transcription unit (with the potential for the addition of a heterologous non-arenavirus polypeptide of interest (hp) downstream in frame with the SP, which is cleaved from the SP by a signal peptidase upon ribosomal translation), and the separation of GP1 / GP2 into a separate transcription unit (in this case, GP1 / GP2 are expressed with an upstream heterologous non-arenavirus signal peptide for ER insertion).

[0134] [Figure 4] Figures 4A-4F: Genomic organization of split-A, split-B, split-C, split-D, split-E, and split-F vector genomes and their X and Y variants. Figures 4A-4F show schematic descriptions of the genomic organization of split-A (Figure 4A), split-B (Figure 4B), split-C (Figure 4C), split-D (Figure 4D), split-E (Figure 4E), and split-F (Figure 4F) vector genomes, each expressing two heterologous non-arenavirus polypeptides ("hp") that can be the same or different from each other. X and Y variants (split-Ax, split-Ay, split-Bx, split-By, etc.) carrying a transgene at only one of the two possible sites are described for each of the genomic configurations shown in Figures 4A-4F.

[0135] [Figure 5]Figure 5: DNA plasmid expression cassettes were used to generate infectious LCMV-based and Junin Candid#1-based split-A, split-C, split-E, and split-F vectors, as well as artLCMV and artCAND vectors, respectively, by transient transfection. Arenavirus RNA genome segments were transcribed from polymerase-I-driven expression cassettes (Pol-IL, Pol-I-S1, Pol-I-S2) consisting of an upstream polymerase-I promoter (pol-IP) and a downstream polymerase-I terminator (pol-IT) flanking the cDNA of the viral segment of interest, including its 5' non-templated G ("G"). The viral segments contain elements outlined in the legends to Figures 1A-1G. The minimal viral transactivators, NP and L, were expressed from plasmids designated pC-NP and pC-L, which contain the actin promoter (Act-P.), the CMV enhancer (CMV-Enh.), and an artificial downstream intron, followed by the cDNA of the viral NP or L protein, respectively, and a polyadenylation site (poly-A).

[0136] [Figure 6]Figures 6A-6E: Comparison of cell culture growth of artLCMV and LCMV-based split-A, split-C, split-E, and split-F vectors. BHK-21 cells expressing LCMV-GP (Flatz L et al., Nat Med 2010;16,339-345) were transfected with the plasmids described in Figure 5 to generate vectors containing the genomes shown in Figures 6A-6B. Replication-competent vector titers in 3T3 cells were determined by immunofocus assay 6 days after transfection. Normal BHK-21 cells (not expressing LCMV-GP) were infected with the viral vectors at an MOI of 0.01, and supernatants were harvested 48 hours later (Figure 6C). Infectious titers were determined by immunofocus assay in 3T3 cells based on the results of one cell culture well (Figures 6B and 6C) or the average of two cell culture wells (Figure 6A). 293F suspension cells (not expressing LCMV-GP) were infected with the viral vectors at an MOI of 0.001, and supernatants were collected at the indicated time points (e.g., 24, 48, 72, 96, or 120 h). The infectious titers were determined in the supernatants by immunofocus assay in 3T3 cells (Figure 6D). The infectious titers of LCMV NP-expressing particles were determined by immunofocus assay using supernatants collected at 48 h (Figure 6D). GP-pseudotimed 293T-GP cells or 3T3 cells were used as cell substrates (values ​​obtained from 3T3 cells are shown in Figure 6D). The ratio of 293T-GP titers to 3T3 titers was calculated for each vector (artLCMV, split-C, and split-E) as a proxy for the ratio of particles packaging all three genome segments (Figure 6E). Filled circles represent independent values ​​obtained from triplicate cell culture wells, and bars indicate the mean + / - standard deviation.

[0137] [Figure 7]Figure 7: Comparison of GFP expression from the split-C vector (TOM / GFP) and the artLCMV vector (TOM / GFP) by fluorescence microscopy. BHK-21 cells were infected with split-C (TOM / GFP) or artLCMV (TOM / GFP). Alternatively, some BHK-21 cells were not infected ("no virus"). 24 hours after infection, green fluorescence was visualized by fluorescence microscopy (Figure 7).

[0138] [Figure 8]Figures 8A-8E: Comparison of GFP and TOM expression from split-C vector (TOM / GFP) and artLCMV vector (TOM / GFP) by flow cytometry. BHK-21 cells were infected with split-C(TOM / GFP) or artLCMV(TOM / GFP) as shown schematically in Figure 8A, or left uninfected ("No virus"; the same experiment as shown in Figure 7). 32 hours after infection, cells were analyzed using flow cytometry analysis of GFP and TOM expression. Separate populations of split-C(TOM / GFP)-infected cells, artLCMV(TOM / GFP)-infected cells, and GFP-expressing cells were gated for further analysis (Figure 8B). For comparison, non-fluorescent uninfected cells were gated (Figure 8B). Graphs showing GFP and TOM fluorescence of cells gated in Figure 8B are shown in Figure 8C. The geometric mean fluorescence intensity of the three cell populations in the GFP and TOM channels, respectively, is shown. Figures 8D–8E show a comparison of GFP and TOM coexpression from the split-C vector (TOM / GFP), GFP and TOM coexpression from the artLCMV vector (TOM / GFP), and GFP and TOM coexpression from the artLCMV vector (GFP / TOM) by flow cytometry. BHK-21 cells were infected with split-C (TOM / GFP), artLCMV (TOM / GFP), or artLCMV (GFP / TOM), whose genomes are shown schematically in Figure 8D, at a multiplicity of infection (MOI) of 0.1. Twenty-four hours postinfection, cells were processed for flow cytometric analysis of GFP and TOM expression (Figure 8E). The percentage of cells exhibiting GFP and / or TOM fluorescence is shown in each quadrant (Figure 8E).

[0139] [Figure 9]Figures 9A-9C: Genetic stability of LCMV-based split-C vectors, but not r3LCMV, in persistently infected AGRAG mice. AGRAG mice were infected intravenously with 10e5 PFU of either an LCMV-based split-C vector (expressing GFP and TOM, the same vector as shown in Figures 7 and 8A-8E), or r3LCMV (GFP) as described in Kallert et al. (Kallert SM et al. (2017) Nat Commun 8, 15327), or a two-segmented wild-type LCMV (genomic organization shown in Figure 1A) based on the Clone 13 backbone and expressing the WE strain glycoprotein. At the indicated time points, blood was collected to determine viral infectivity by detecting either viral NP (as a measure of overall infectivity, Figure 9A) or the GFP transgene (as a measure of transgene expression infectivity, Figure 9B). The ratio of NP infectivity to GFP infectivity was then calculated (Figure 9C). Figures 9D-9F: Genetic stability of LCMV-based split-C and artLCMV vectors, but not r3LCMV, in persistently infected AGRAG mice. AGRAG mice were infected intravenously with 10e5 PFU of either i) a GFP-expressing LCMV-based split-C vector (split-C(GFP)), ii) artLCMV(GFP), iii) r3LCMV(GFP) (as described in Kallert et al. (2017) Nat Commun 8, 15327), or iv) a two-segmented wild-type LCMV (genome organization shown in Figure 1A) based on the Clone 13 backbone and expressing the WE strain glycoprotein. At the indicated time points, blood was collected to determine viral infectivity by detecting either viral NP (as a measure of overall infectivity, Figure 9D) or the GFP transgene (as a measure of transgene expression infectivity, Figure 9E). The ratio of NP infectivity:GFP infectivity was then calculated (Figure 9F). Symbols first show the mean + / - SEM of 3 (LCMVwt), 5 (r3LCMV(GFP)), 4 (artLCMV(GFP)), and 6 (split-C) animals.

[0140] [Figure 10] Figures 10A-10D: Immunogenicity of cancer-testis antigens expressed from the S1 segment of LCMV-based split-C vectors compared to the SGP segment of artLCMV. BALB / c mice were immunized with 5x10e5 PFU of either an LCMV-based split-C vector expressing GFP and the cancer-testis antigen P1A or an artLCMV vector delivering the same transgene (i.e., the cancer-testis antigen P1A). The respective vector genomes are shown in Figure 10A. Nine days after immunization, the P1A-derived [ka] MHC class I tetramers (H-2Ld) loaded with peptide epitopes (Figure 10B) or immunodominant NP-derived scaffold epitopes [ka] CD8+ T cell responses were determined in peripheral blood using a P1A-loaded MHC class I tetramer (H-2Ld) (NP118, Figure 10C). The ratio of P1A-specific CD8+ T cells to NP118-specific CD8+ T cells was calculated for each mouse as a measure of transgene immunodominance (Figure 10D). Statistical significance was determined using an unpaired, two-tailed Student's t-test. ** : p<0.01, ns: p>0.05.

[0141] [Figure 11]Figures 11A-11N: Immunogenicity of the artificial HPV16 E7E6 fusion antigen expressed from the S1 segment of an LCMV-based split-C vector compared to the SGP segment of artLCMV. C57BL / 6 mice were immunized with either 10e5 PFU of an LCMV-based split-C vector expressing GFP and an artificial HPV16 E7E6 fusion antigen or an artLCMV vector delivering the same transgene (i.e., GFP and an artificial HPV16 E7E6 fusion antigen). The respective vector genomes are shown in Figure 11A. Control mice were maintained without immunization ("none"). Eight days after immunization, CD8+ T cell responses were determined in peripheral blood, and 22 days after immunization, CD8+ T cell responses were determined in the spleen. In this experiment, CD8+ T cell responses derived from the HPV16 E7 protein were measured. [ka] MHC class I dextramer (H-2Db) loaded with peptide epitopes (E7-Dex, Figures 11B, 11E, 11H, and 11J-11N) or immunodominant NP-derived backbone epitopes [ka] MHC class I dextramer (H-2Db) loaded with E7-Dex (NP396-Tet, Figures 11C, 11F, and 11I) was used. The ratio of P1A-specific CD8+ T cells to NP118-specific CD8+ T cells was calculated as a measure of transgene immunodominance (Figures 11D and 11G). The frequencies of E7-Dex+ and NP396-Tet+ cells are expressed as a percentage of CD8+ B220- cells (Figures 11B, 11C, 11E, and 11F). The absolute numbers of E7-Dex+ or NP396-Tet+ CD8+ B220- cells per spleen are shown in Figures 11H and 11I. The subsets of E7-Dex+ CD8+ B220- cells expressing the indicated markers are listed in Figures 11J–11N). Statistical significance was determined using an unpaired, two-tailed Student's t-test. ** : p<0.01, * : p<0.05, ns: p>0.05.

[0142] [Figure 12] Figures 12A-12C: Evaluation of cell culture growth of split-C-CAND vectors. BHK-21 cells expressing LCMV-GP (Flatz L et al., Nat Med 2010;16, 339-345) were transfected with the plasmids described in Figure 5 to generate split-C-CAND(TOM / GFP) and split-C-CAND(TOM / E7E6) vectors containing the genomes shown in Figures 12A-12B. Five days after transfection, supernatants were blindly passaged onto normal 293T cells (which do not express LCMV-GP). Culture supernatants were harvested 2, 7, and 9 days after seeding, and replication-competent vector titers were determined in 3T3 cells (Figure 12C).

[0143] [Figure 13] Figures 13A-13D: Comparison of GFP and TOM expression from split-C-CAND (TOM / GFP) and artCAND vector (TOM / GFP) by flow cytometry. 293T cells were infected with split-C-CAND (TOM / GFP) or artCAND (TOM / GFP) as shown schematically in Figure 13A, or left uninfected ("no virus"). 72 hours after infection, cells were analyzed for GFP and TOM using flow cytometry (Figures 13B-13D). When GFP and TOM were plotted against side scatter, distinct populations of cells expressing GFP (Figure 13C) or TOM (Figure 13D) were detected in split-C-CAND (TOM / GFP)- and artCAND (TOM / GFP)-infected cell cultures but not in uninfected control cell cultures (SSC-H; Figures 13C-13D). GFP mean fluorescence intensity (MFI; FIG. 13C) and TOM MFI (FIG. 13D) of virus-infected cultures are shown.

[0144] [Figure 14]Figures 14A-14D: Immunogenicity of an artificial HPV16 E7E6 fusion antigen expressed from the S1 segment of a CAND-based split-C vector compared to the SGP segment of artCAND. C57BL / 6 mice were immunized with either 2x10e5 FFU of a CAND-based split-C vector expressing TOM and an artificial fusion antigen consisting of the E7 and E6 proteins of HPV16 (Cassetti et al., Vaccine 2004; 3-4, 520-527) (split-C-CAND(TOM / E7E6)) or an artCAND vector delivering the same transgenes (i.e., TOM and E7E6) (artCAND(TOM / E7E6)). The respective vector genomes are shown in Figure 14A. Nine days after immunization, CD8+ T cell responses were elicited using a fusion antigen derived from the HPV16 E7 protein. [ka] Peptide epitope-loaded MHC class I dextramer (H-2Db) (E7-Dex, Figure 14B) and NP-derived backbone epitopes [ka] The expression of E7-specific CD8+ T cells was determined in peripheral blood using a NP205-loaded MHC class I tetramer (H-2Kb) (NP205, Figure 14C). The ratio of E7-specific CD8+ T cells to NP205-specific CD8+ T cells was calculated for each mouse as a measure of transgene immunodominance (Figure 14D). Statistical significance was determined using an unpaired two-tailed Student's t-test. ** : p<0.01, ns: p>0.05. DETAILED DESCRIPTION OF THE INVENTION

[0145] (5. Detailed Description of the Invention) Provided herein are arenavirus particles that are genetically stable and result in high levels of transgene expression. In certain embodiments, the arenavirus particles are trisegmented. Also provided herein are nucleotide sequences and arenavirus genome or antigenome segments associated with such arenavirus particles. In certain embodiments, provided herein are nucleotide sequences (see Section 5.4) comprising one or more ORFs that comprise nucleotide sequences encoding functional fragments (see Section 5.2) of arenavirus GP, NP, L, or Z (see Section 5.1) and / or heterologous non-arenavirus polypeptides (see Section 5.3). In certain embodiments, provided herein are arenavirus particles modified such that arenavirus ORFs are spaced across two or more mRNA transcripts (see Section 5.5). In certain embodiments, provided herein are arenavirus genome or antigenome segments modified such that transcription produces one or more mRNA transcripts that comprise nucleotide sequences encoding functional fragments of arenavirus GP, NP, L, or Z (see Section 5.6). In certain embodiments, the arenavirus particles provided herein are genetically stable, i.e., do not revert to wild-type (more virulent) replication behavior in a host (genetic stability) (see Section 5.13). In certain embodiments, the arenavirus particles provided herein can exhibit high levels of transgene expression (transgene expression levels) to elicit a strong immune response against a desired target antigen (see Section 5.13). In certain embodiments, the arenavirus particles provided herein can exhibit good growth in cell culture, enabling production of arenavirus particles to high titers (production yields) in industrial fermentation processes (see Section 5.13). In certain embodiments, the arenavirus particles provided herein can be suitable for use as vaccines, for treating disease, and / or in immunotherapy (see Sections 5.11 and 5.12).

[0146] Arenaviruses for use with the methods and compositions provided herein can be, for example, Old World viruses such as Lassa virus, lymphocytic choriomeningitis virus (LCMV), Mobara virus, Mopeia virus, or Yippie virus, or New World viruses such as Amapari virus, Flexar virus, Guanarito virus, Junin virus, Latino virus, Machupo virus, Oliveros virus, Parana virus, Piquinde virus, Piritar virus, Sabia virus, Tacaribe virus, Tamiami virus, Bear Canyon virus, Alpahuayo virus (ALLV), or Whitewater Arroyo virus. Arenaviruses for use with the methods and compositions provided herein can be, for example, arenaviruses, mammarenaviruses, Old World mammarenaviruses, New World mammarenaviruses, clade A New World mammarenaviruses, clade B New World mammarenaviruses, clade C New World mammarenaviruses, or clade D New World mammarenaviruses. Arenaviruses for use with the methods and compositions provided herein include, but are not limited to, Alpahuayo virus, Arxa virus, Junin virus, Bear Canyon virus, Sabia virus, Piquinde virus, Chapare virus, Lijiang virus, Cupixi virus, Flexar virus, Gairo virus, Ganarito virus, Yippi virus, Lassa virus, Latino virus, Loui River virus, Lujo virus, Luna virus, Luli virus, Runku virus, Lymphocytic choriomeningitis virus, Machupo virus, Marienta virus, and others. The virus may be a Mammalenavirus, including a virus such as Arle virus, Merinowalk virus, Mobara virus, Mopeia virus, Morogoro virus, Okahandja virus, Oliveros virus, Parana virus, Piritar virus, Apore virus, Ryukyu virus, Amapari virus, Solwezi virus, Thule virus, Tacaribe virus, Tamiami virus, Unshu virus, Whitewater Arroyo virus, Big Brushy Tank virus, Catalina virus, Skinner Tank virus, Tonto River virus, or Shapuli virus.

[0147] 5.1 Polypeptides Selected from the Group Consisting of Arenavirus GP, NP, Z, and L In certain embodiments, provided herein are nucleotide sequences comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of a polypeptide. In certain embodiments, provided herein are arenavirus genome or antigenome segments modified such that transcription thereof produces one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of a polypeptide. In certain embodiments, the polypeptides described herein are selected from the group consisting of arenavirus GP, NP, Z, and L, i.e., arenavirus glycoprotein, nucleoprotein, Z protein, L protein, glycoprotein precursor, nucleoprotein precursor, Z protein precursor, and L protein precursor. In certain embodiments, arenavirus GP, NP, Z, and L are wild-type. In other embodiments, arenavirus GP, NP, Z, and L are recombinant. In certain embodiments, arenavirus GP, NP, Z, and L are mutant. In certain embodiments, arenavirus GP, NP, Z, and L are derived from an attenuated virus.

[0148] In certain embodiments, the polypeptides described herein are selected from the group consisting of wild-type arenavirus glycoprotein, nucleoprotein, Z protein, L protein, glycoprotein precursor, nucleoprotein precursor, Z protein precursor, and L protein precursor. In certain embodiments, the polypeptides described herein are wild-type arenavirus glycoprotein precursor. In certain embodiments, the wild-type arenavirus glycoprotein precursor can be processed into a GP signal peptide, GP1, and GP2.

[0149] In certain embodiments, the polypeptides described herein are selected from the group consisting of recombinant arenavirus glycoproteins, nucleoproteins, Z proteins, L proteins, glycoprotein precursors, nucleoprotein precursors, Z protein precursors, and L protein precursors. In certain embodiments, the polypeptides described herein are recombinant arenavirus glycoprotein precursors. In certain embodiments, the recombinant arenavirus glycoprotein precursors can be processed into GP signal peptides, GP1, and GP2, one or more of which are recombinant.

[0150] In certain embodiments, the polypeptides described herein are selected from the group consisting of a mutant arenavirus glycoprotein, nucleoprotein, Z protein, L protein, glycoprotein precursor, nucleoprotein precursor, Z protein precursor, and L protein precursor. In certain embodiments, the polypeptides described herein are mutant arenavirus glycoprotein precursors. In certain embodiments, the mutant arenavirus glycoprotein precursors can be processed into GP signal peptides, GP1, and GP2, one or more of which are mutated.

[0151] In certain embodiments, the polypeptides described herein are selected from the group consisting of arenavirus glycoproteins, nucleoproteins, Z proteins, L proteins, glycoprotein precursors, nucleoprotein precursors, Z protein precursors, and L protein precursors derived from an attenuated virus. In certain embodiments, the polypeptides described herein are arenavirus glycoprotein precursors derived from an attenuated virus. In certain embodiments, the arenavirus glycoprotein precursors can be processed into GP signal peptides, GP1, and GP2, one or more of which are derived from the attenuated virus.

[0152] In some embodiments, the polypeptide described herein is selected from the group consisting of GP, NP, Z, and L of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Ruri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0153] In certain embodiments, the polypeptides described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO: SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77 , SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptide described herein is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134 , SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108,. In certain embodiments, the polypeptides described herein comprise an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, the polypeptides described herein comprise an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO: 77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the polypeptides described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO: 49, SEQ ID NO: 56, SEQ ID NO: 63, SEQ ID NO: 70, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 88, SEQ ID NO: 95, SEQ ID NO: 102, SEQ ID NO: 106, SEQ ID NO: 110, SEQ ID NO: 117, SEQ ID NO: 124, SEQ ID NO: 131, SEQ ID NO: 138, SEQ ID NO: 50, SEQ ID NO: 57, SEQ ID NO: 64, SEQ ID NO: 71, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 89, SEQ ID NO: 96, SEQ ID NO: 103, SEQ ID NO: 107, SEQ ID NO: 111, SEQ ID NO: 118, SEQ ID NO: 125, SEQ ID NO: 132, SEQ ID NO: 139, SEQ ID NO: 51, SEQ ID NO: 58, SEQ ID NO: 65, SEQ ID NO: 72, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO: 90, SEQ ID NO: 97, SEQ ID NO: 104, SEQ ID NO: 108, SEQ ID NO: SEQ ID NO: 112, SEQ ID NO: 119, SEQ ID NO: 126, SEQ ID NO: 133, or SEQ ID NO: 140.

[0154] In certain embodiments, the polypeptides described herein are arenavirus GPs, i.e., arenavirus glycoproteins or any glycoprotein precursors. In certain embodiments, the polypeptides described herein are wild-type arenavirus glycoproteins or any wild-type glycoprotein precursors. In other embodiments, the polypeptides described herein are recombinant arenavirus glycoproteins or any recombinant glycoprotein precursors. In certain embodiments, the arenavirus glycoprotein precursors can be processed into the GP signal peptide, GP1, and GP2. In certain embodiments, the arenavirus GP is an arenavirus glycoprotein or any glycoprotein precursor of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexar virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuayo virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134. In certain embodiments, a GP described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, a GP described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO: 134. In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.In certain embodiments, an arenavirus GP described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, or SEQ ID NO:134.

[0155] In certain embodiments, the polypeptides described herein are arenavirus NP, i.e., arenavirus nucleoprotein or any nucleoprotein precursor. In certain embodiments, the polypeptides described herein are wild-type arenavirus nucleoprotein or any wild-type nucleoprotein precursor. In other embodiments, the polypeptides described herein are recombinant arenavirus nucleoprotein or any recombinant nucleoprotein precursor. In certain embodiments, the arenavirus NP is an arenavirus nucleoprotein or any nucleoprotein precursor of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexar virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO: 138. In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.In certain embodiments, an arenavirus NP described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, or SEQ ID NO:138.

[0156] In certain embodiments, the polypeptides described herein are arenavirus Z, i.e., arenavirus Z protein or any Z protein precursor. In certain embodiments, the polypeptides described herein are wild-type arenavirus Z protein or any wild-type Z protein precursor. In other embodiments, the polypeptides described herein are recombinant arenavirus Z protein or any recombinant Z protein precursor. In some embodiments, the arenavirus Z is an arenavirus Z protein or any Z protein precursor of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexar virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuayo virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, an arenavirus Z described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.In certain embodiments, the arenavirus Z described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, or SEQ ID NO:139.

[0157] In certain embodiments, the polypeptides described herein are arenavirus L, i.e., arenavirus L protein or any L protein precursor. In certain embodiments, the polypeptides described herein are wild-type arenavirus L protein or any wild-type L protein precursor. In other embodiments, the polypeptides described herein are recombinant arenavirus L protein or any recombinant L protein precursor. In certain embodiments, the arenavirus L is an arenavirus L protein or any L protein precursor of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexar virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuayo virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO: 140. In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, an arenavirus L described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.

[0158] 5.2 Functional Fragments Provided Herein Functional fragments to be used in the compositions and methods described herein are fragments of polypeptides. Functional fragments of the polypeptides described herein are not the full-length polypeptides.

[0159] In certain embodiments, the functional fragment may retain one or more functions known to those of skill in the art. In certain embodiments, the functional fragment may retain a biological function of the polypeptide from which it is derived, such as a biological function required for the propagation of arenavirus particles. In certain embodiments, the functional fragment can support the biological function of the polypeptide from which it is derived as an isolated fragment independent of the context of the full-length polypeptide. In an exemplary embodiment, the functional fragment may be a signal peptide that retains the function of mediating insertion of a glycoprotein precursor into the endoplasmic reticulum (ER) membrane. In further embodiments, in addition to mediating insertion of a glycoprotein precursor into the ER membrane, the signal peptide may retain other functions, such as mediating cleavage of the polypeptide and / or acting as a trans-acting maturation factor. In other embodiments, the functional fragment may not retain any functions known to those of skill in the art.

[0160] In certain embodiments, the functional fragment may be 5, 8, 10, 12, 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 amino acids in length. In certain embodiments, the functional fragment is 5 to 10 amino acids long, 10 to 25 amino acids long, 25 to 50 amino acids long, 50 to 100 amino acids long, 100 to 150 amino acids long, 150 to 200 amino acids long, 200 to 250 amino acids long, 250 to 300 amino acids long, 300 to 400 amino acids long, 400 to 500 amino acids long, 500 to 750 amino acids long, 750 to 1000 amino acids long, 1000 to 1250 amino acids long, 1250 to 1500 amino acids long, 1500 to 1750 amino acids long, 1750 to 2000 amino acids long, 2000 to 2500 amino acids long, or more than 2500 amino acids long. In certain embodiments, the functional fragment is no longer than 2500 amino acids.

[0161] In certain embodiments, the functional fragment may consist of 5, 8, 10, 12, 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, or 300 amino acid residues. In certain embodiments, the functional fragment may consist of 58 amino acid residues. In certain embodiments, the functional fragment may consist of 193 amino acid residues. In certain embodiments, the functional fragment may consist of 200 amino acid residues. In certain embodiments, the functional fragment may consist of 201 amino acid residues. In certain embodiments, the functional fragment may consist of 207 amino acid residues. In certain embodiments, the functional fragment may consist of 215 amino acid residues. In certain embodiments, the functional fragment may consist of 225 amino acid residues. In certain embodiments, the functional fragment may consist of 232 amino acid residues. In certain embodiments, the functional fragment may consist of 233 amino acid residues. In certain embodiments, the functional fragment may consist of 234 amino acid residues. In certain embodiments, the functional fragment may consist of 235 amino acid residues. In certain embodiments, the functional fragment may consist of 15 amino acid residues. In certain embodiments, the functional fragment may consist of 20 amino acid residues. In certain embodiments, the functional fragment may consist of 1 to 15 amino acid residues. In certain embodiments, the functional fragment may consist of 2 to 20 amino acid residues.

[0162] In certain embodiments, the functional fragment is a fragment of arenavirus GP, NP, Z, or L, i.e., a fragment of arenavirus glycoprotein, nucleoprotein, Z protein, L protein, glycoprotein precursor, nucleoprotein precursor, Z protein precursor, or L protein precursor. In certain embodiments, the functional fragment of arenavirus GP, NP, Z, or L is wild-type. In other embodiments, the functional fragment of arenavirus GP, NP, Z, and L is recombinant. In certain embodiments, the functional fragment of arenavirus GP, NP, Z, or L is mutant. In certain embodiments, the functional fragment of arenavirus GP, NP, Z, or L is derived from an attenuated virus.

[0163] In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus glycoprotein, nucleoprotein, Z protein, or L protein. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus glycoprotein. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus nucleoprotein. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus Z protein. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus L protein.

[0164] In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus glycoprotein precursor, nucleoprotein precursor, Z protein precursor, or L protein precursor. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus glycoprotein precursor. In certain embodiments, the wild-type arenavirus glycoprotein precursor can be processed into a GP signal peptide, GP1, and GP2. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus nucleoprotein precursor. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus Z protein precursor. In certain embodiments, the functional fragment is a fragment of a wild-type arenavirus L protein precursor.

[0165] In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus glycoprotein, nucleoprotein, Z protein, or L protein. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus glycoprotein. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus nucleoprotein. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus Z protein. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus L protein.

[0166] In certain embodiments, the functional fragment is a recombinant arenavirus glycoprotein precursor, nucleoprotein precursor, Z protein precursor, or L protein precursor. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus glycoprotein precursor. In certain embodiments, the arenavirus glycoprotein precursor can be processed into the GP signal peptide, GP1, and GP2, one or more of which can be recombinant. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus nucleoprotein precursor. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus Z protein precursor. In certain embodiments, the functional fragment is a fragment of a recombinant arenavirus L protein precursor.

[0167] In certain embodiments, the functional fragment is a fragment of a mutant arenavirus glycoprotein, nucleoprotein, Z protein, or L protein. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus glycoprotein. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus nucleoprotein. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus Z protein. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus L protein.

[0168] In certain embodiments, the functional fragment is a mutant arenavirus glycoprotein precursor, nucleoprotein precursor, Z protein precursor, or L protein precursor. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus glycoprotein precursor. In certain embodiments, the arenavirus glycoprotein precursor can be processed into GP signal peptide, GP1, and GP2, one or more of which can be mutated. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus nucleoprotein precursor. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus Z protein precursor. In certain embodiments, the functional fragment is a fragment of a mutant arenavirus L protein precursor.

[0169] In certain embodiments, the functional fragment is a fragment of an arenavirus glycoprotein, nucleoprotein, Z protein, or L protein derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus glycoprotein derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus nucleoprotein derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus Z protein derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus L protein derived from an attenuated virus.

[0170] In certain embodiments, the functional fragment is an arenavirus glycoprotein precursor, nucleoprotein precursor, Z protein precursor, or L protein precursor derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus glycoprotein precursor derived from an attenuated virus. In certain embodiments, the arenavirus glycoprotein precursor can be processed into a GP signal peptide, GP1, and GP2, one or more of which are derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus nucleoprotein precursor derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus Z protein precursor derived from an attenuated virus. In certain embodiments, the functional fragment is a fragment of an arenavirus L protein precursor derived from an attenuated virus.

[0171] In certain embodiments, the functional fragment is a fragment of an arenavirus glycoprotein precursor. In certain embodiments, the functional fragment is an arenavirus GP signal peptide. In certain embodiments, the arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, the arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135.In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, the arenavirus GP signal peptide described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135.In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, the arenavirus GP signal peptide described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135.In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO: 135. In certain embodiments, an arenavirus GP signal peptide described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:53, SEQ ID NO:60, SEQ ID NO:67, SEQ ID NO:74, SEQ ID NO:85, SEQ ID NO:92, SEQ ID NO:99, SEQ ID NO:114, SEQ ID NO:121, SEQ ID NO:128, or SEQ ID NO:135.

[0172] In certain embodiments, the functional fragment is GP1. In certain embodiments, GP1 described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, the arenavirus GP1 described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136.In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, the arenavirus GP1 described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136.In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, the arenavirus GP1 described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136.In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO: 136. In certain embodiments, an arenavirus GP1 described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, or SEQ ID NO:136.

[0173] In certain embodiments, the functional fragment is GP2. In certain embodiments, the GP2 described herein comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, the arenavirus GP2 described herein comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, the arenavirus GP2 described herein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, the arenavirus GP2 described herein comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 85% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 90% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 95% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, the arenavirus GP2 described herein comprises an amino acid sequence that is 96% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 97% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO: 137. In certain embodiments, an arenavirus GP2 described herein comprises an amino acid sequence that is 98% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137. In certain embodiments, the arenavirus GP2 described herein comprises an amino acid sequence that is 99% identical to the amino acid sequence of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:69, SEQ ID NO:76, SEQ ID NO:87, SEQ ID NO:94, SEQ ID NO:101, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:130, or SEQ ID NO:137.

[0174] In certain embodiments, the functional fragment may consist of more than one of the GP signal peptide, GP1, and GP2. In certain embodiments, the functional fragment may consist of the GP signal peptide and GP1. In certain embodiments, the functional fragment may consist of the GP signal peptide and GP2. In certain embodiments, the functional fragment may consist of GP1 and GP2. In certain embodiments, the functional fragment is not a full-length glycoprotein precursor.

[0175] In some embodiments, the functional fragment is a fragment of an arenavirus GP signal peptide. In some embodiments, the arenavirus GP signal peptide is wild-type. In other embodiments, the arenavirus GP signal peptide is recombinant. In certain embodiments, the arenavirus GP signal peptide is selected from the group consisting of a GP signal peptide of LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexar virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner's Tank virus, Tonto River virus, Shapuli virus, or Junin virus. In certain embodiments, the functional fragment is selected from the group consisting of the n region, hydrophobic region 1 (h-1 region), and hydrophobic region 2 (h-2 region) of an arenavirus GP signal peptide. In certain embodiments, the functional fragment is the n region of an arenavirus GP signal peptide. In certain embodiments, the functional fragment is the h-1 region of an arenavirus GP signal peptide. In certain embodiments, the functional fragment is the h-2 region of an arenavirus GP signal peptide.

[0176] In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:122, SEQ ID NO:130, SEQ ID NO:144, SEQ ID NO:156, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, SEQ ID NO:170, SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO:174, SEQ ID NO:175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO:178, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO:181, SEQ No. 109, SEQ ID NO: 113, SEQ ID NO: 120, SEQ ID NO: 127, SEQ ID NO: 134, SEQ ID NO: 49, SEQ ID NO: 56, SEQ ID NO: 63, SEQ ID NO: 70, SEQ ID NO: 77, SEQ ID NO: 81, SEQ ID NO: 88, SEQ ID NO: 95, SEQ ID NO: 102, SEQ ID NO: 106, SEQ ID NO: 110, SEQ ID NO: 117, SEQ ID NO: 124, SEQ ID NO: 131, SEQ ID NO: 138, SEQ ID NO: 50, SEQ ID NO: 57, SEQ ID NO: 64, SEQ ID NO: 71, SEQ ID NO: 78, SEQ ID NO: 82, SEQ ID NO: 89, SEQ ID NO: 96, SEQ ID NO: 103, SEQ ID NO: 107, SEQ ID NO: 111, SEQ ID NO: 118, SEQ ID NO: 125, SEQ ID NO: 132, SEQ ID NO: 139. A fragment of a polypeptide comprising an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO: SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.

[0177] In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, and a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:111, SEQ ID NO:122, SEQ ID NO:13, SEQ ID NO:143, SEQ ID NO:154, SEQ ID NO:165, SEQ ID NO:176, SEQ ID NO:187, SEQ ID NO:198, SEQ ID NO:209, SEQ ID NO:210, SEQ ID NO:211, SEQ ID NO:223, SEQ ID NO:244, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:599, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111 Sequence number 91, sequence number 98, sequence number 105, sequence number 109, sequence number 113, sequence number 120, sequence number 127, sequence number 134, sequence number 49, sequence number 56, sequence number 63, sequence number 70, sequence number 77, sequence number 81, sequence number 88, sequence number 95, sequence number 102, sequence number 106, sequence number 110, sequence number 117, sequence number 124, sequence number 131, sequence number 138, sequence number 50, sequence number 57, sequence number 64, sequence number 71, sequence number 78, sequence number 82, sequence number 89, sequence number 96, sequence number 103. , SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140. In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.In certain embodiments, the functional fragments described herein are SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81 , SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140.

[0178] 5.3 Heterologous Non-Arenavirus Polypeptides As described herein, in certain embodiments, a heterologous non-arenavirus polypeptide may not be of arenavirus origin.

[0179] In certain embodiments, the nucleotide sequences provided herein (see Section 5.4) comprise a first open reading frame (ORF) comprising a nucleotide sequence encoding a functional fragment of a first polypeptide selected from the group consisting of arenavirus GP, NP, Z, and L, and a second ORF comprising a nucleotide sequence encoding a heterologous non-arenavirus polypeptide provided herein. In certain embodiments, the nucleotide sequences provided herein comprise an open reading frame (ORF) comprising a nucleotide sequence encoding a functional fragment of a first polypeptide selected from the group consisting of arenavirus GP, NP, Z, and L that is not derived from a Lassa virus, and a heterologous non-arenavirus polypeptide. In certain embodiments, the arenavirus particles described herein are of arenavirus origin, but the arenavirus particle comprises a genome encoding a heterologous polypeptide derived from a type of arenavirus different from the type of arenavirus that comprises GP, NP, Z, and L. In exemplary embodiments, the heterologous polypeptide is derived from a Lassa virus, but the arenavirus particle comprises GP, NP, Z, and L of an LCMV or Pikinde virus.

[0180] In certain embodiments, the arenavirus particles provided herein are engineered so that the arenavirus ORFs are spaced across two or more mRNA transcripts (see Section 5.5). In certain embodiments, one of the mRNA transcripts further comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide. In certain embodiments, one of the mRNA transcripts is of arenavirus origin, but further comprises a nucleotide sequence encoding a heterologous polypeptide derived from a type of arenavirus different from the type of arenavirus that comprises GP, NP, Z, and L. In exemplary embodiments, the heterologous polypeptide is derived from Lassa virus, but the arenavirus particle comprises GP, NP, Z, and L of LCMV or Pikinde virus.

[0181] In certain embodiments, the arenavirus genome or antigenome segments provided herein (see Section 5.6) are engineered such that viral transcription produces a first mRNA transcript comprising a nucleotide sequence encoding a functional fragment of a first polypeptide selected from the group consisting of arenavirus GP, NP, Z, and L, and a second mRNA transcript comprising a nucleotide sequence encoding a heterologous non-arenavirus polypeptide. In certain embodiments, the arenavirus genome or antigenome segments provided herein are engineered such that viral transcription produces an mRNA transcript encoding a functional fragment of a first polypeptide selected from the group consisting of arenavirus GP, NP, Z, and L, and a heterologous non-arenavirus polypeptide or a second polypeptide. In certain embodiments, the arenavirus genome or antigenome segments provided herein are engineered such that viral transcription produces an mRNA transcript encoding a functional fragment of a first polypeptide selected from the group consisting of arenavirus GP, NP, Z, and L, and a heterologous polypeptide that is of arenavirus origin but is derived from a type of arenavirus different from the type of arenavirus comprising GP, NP, Z, and L. In exemplary embodiments, the heterologous polypeptide is from a Lassa virus, while the arenavirus genome includes the GP, NP, Z, and L of an LCMV or Pikinde virus.

[0182] In certain embodiments, the heterologous non-arenavirus polypeptide is about, at most about, or at least about 5, 8, 10, 12, 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, or more than 1000 amino acids in length. In certain embodiments, the heterologous non-arenavirus polypeptide is about, at least about, or at most about 5-10 amino acids in length, 10-25 amino acids in length, 25-50 amino acids in length, 50-100 amino acids in length, 100-150 amino acids in length, 150-200 amino acids in length, 200-250 amino acids in length, 250-300 amino acids in length, 300-400 amino acids in length, 300-500 amino acids in length, 350-600 amino acids in length, 400-500 amino acids in length, 500-750 amino acids in length, 750-1000 amino acids in length, 1000-1250 amino acids in length, 1250-1500 amino acids in length, 1500-1750 amino acids in length, 1750-2000 amino acids in length, 2000-2500 amino acids in length, or more than 2500 or more amino acids in length. In certain embodiments, the heterologous non-arenavirus polypeptide is no more than 500 amino acids in length. In certain embodiments, the heterologous non-arenavirus polypeptide is no more than 750 amino acids in length. In certain embodiments, the heterologous non-arenavirus polypeptide is no more than 1000 amino acids in length. In certain embodiments, the heterologous non-arenavirus polypeptide is no more than 2500 amino acids in length.

[0183] In certain embodiments, the heterologous non-arenavirus polypeptide consists of about, at least about, or at most about 5, 8, 10, 12, 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 58 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 193 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 200 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 480 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 450 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 500 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 350 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 400 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 550 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 600 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 15 amino acid residues. In certain embodiments, the heterologous non-arenavirus polypeptide may consist of about, at least about, or at most about 20 amino acid residues.In certain embodiments, the heterologous non-arenavirus polypeptide can consist of about, at least about, or at most about 1 to 20 amino acid residues, hi certain embodiments, the heterologous non-arenavirus polypeptide can consist of about, at least about, or at most about 200 to 600 amino acid residues.

[0184] In certain embodiments, the heterologous non-arenavirus polypeptide is a reporter protein (see Section 5.3.1). In certain embodiments, the heterologous non-arenavirus polypeptide is a heterologous non-arenavirus signal peptide (see Section 5.3.2). In certain embodiments, the heterologous non-arenavirus polypeptide is an antigen (see Section 5.3.3).

[0185] 5.3.1 Reporter Proteins In certain embodiments, the heterologous non-arenavirus polypeptide described herein is a reporter protein or a fluorescent protein. In certain embodiments, the reporter protein is a fluorescent protein. In certain embodiments, the reporter protein is green fluorescent protein (GFP). GFP emits bright green light when exposed to UV or blue light. In other embodiments, the reporter protein is red fluorescent protein (RFP). In an exemplary embodiment, the reporter protein is TOM.

[0186] Reporter proteins and genes will be readily recognized by those skilled in the art. Non-limiting examples of reporter proteins include various enzymes, such as, but not limited to, β-galactosidase, chloramphenicol acetyltransferase, neomycin phosphotransferase, luciferase, or RFP.

[0187] In some embodiments, the reporter protein can be expressed simultaneously with the antigen described herein. Ideally, the expression is visible under normal light or other wavelengths of light. In some embodiments, the intensity of the effect produced by the reporter protein can be used to directly measure and monitor arenavirus particles or three-segmented arenavirus particles.

[0188] 5.3.2 Heterologous Non-Arenavirus Signal Peptides In certain embodiments, the heterologous non-arenavirus polypeptide described herein is a heterologous non-arenavirus signal peptide. In certain embodiments, the heterologous non-arenavirus signal peptide is a signal peptide of a glycoprotein. In certain embodiments, the heterologous non-arenavirus signal peptide is a signal peptide of a glycoprotein from Adenoviridae (e.g., mastadenovirus and aviadenovirus), Herpesviridae (e.g., herpes simplex virus type 1, herpes simplex virus type 2, herpes simplex virus type 5, herpes simplex virus type 6, Epstein-Barr virus, HHV6-HHV8, cytomegalovirus, and varicella-zoster virus), Leviviridae (e.g., levivirus, enteric bacteriophage MS2, allorevirus), or other viruses. viruses), Orthomyxoviridae (e.g., influenza A virus, influenza B virus, influenza C virus), Parvoviridae (e.g., parvovirus B19), Filoviridae (e.g., Ebola virus, Marburg virus), Hantaviridae, Poxviridae (e.g., chordopoxviridae, parapoxvirus, avipoxvirus, capripoxvirus, leporipoxvirus, suipoxvirus, morsipovirus, and Entomopoxvirinae), Polyomaviridae, Papillomaviridae (e.g., human papillomavirus), Paramyxoviridae (e.g., paramyxoviruses, parainfluenza virus type 1, mobiliviruses (e.g., measles virus), rubulaviruses (e.g., mumps virus)), Pneumoviridae (e.g., pneumoviruses, human respiratory syncytial viruses, and metapneumoviruses (e.g., avian pneumovirus and human metapneumovirus)), Picornaviridae (e.g., enteroviruses, rhinoviruses, hepatoviruses (e.g., human hepatitis A virus), cardioviruses, and aphthoviruses), Reoviridae (e.g., orthoreoviruses, orbiviruses, rotaviruses, cypoviruses, phyziviruses, phytreoviruses, and oryzaviruses), Retroviridae (e.g., mammalian type B retroviruses, mammalian type C retroviruses, avian type C retroviruses, type D retrovirus group,BLV-HTLV retroviruses, lentiviruses (e.g., human immunodeficiency virus (HIV) 1 and HIV-2 (e.g., HIV gp160)), spumaviruses), Flaviviridae (e.g., hepatitis C virus, dengue virus, West Nile virus), Hepadnaviridae (e.g., hepatitis B virus), Togaviridae (e.g., alphaviruses (e.g., Sindbis virus) and rubiviruses (e.g., rubella virus)), Rhabdoviridae (e.g., vesiculoviruses, lyssaviruses, ephemeloviruses, cytorhabdoviruses, and nucleorhabdoviruses), Arenaviridae (e.g., arenaviruses, lymphocytic choriomeningitis virus, Yippie virus), , Mobaravirus, Mopeiavirus, Amaparivirus, Flexarvirus, Gunaritovirus, Juninvirus, Latinovirus, Machupovirus, Oliverosvirus, Paranavirus, Piquindevirus, Piritarvirus, Sabiavirus, Tacaribevirus, Tamiamivirus, Bear Canyonvirus, Whitewater Arroyovirus, Alpahuayovirus (ALLV), and Lassavirus), and the Coronaviridae family (e.g., coronavirus and torovirus). In one embodiment, the heterologous non-arenavirus signal peptide is the signal peptide of vesicular stomatitis virus serotype Indiana glycoprotein.

[0189] (5.3.3 Antigen) In certain embodiments, the heterologous non-arenavirus polypeptide is an antigen. In certain embodiments, the antigen is derived from an infectious organism, a tumor, or an allergen. In one embodiment, the antigen is of an infectious pathogen or is associated with any disease capable of eliciting an immune response. In certain embodiments, the heterologous non-arenavirus polypeptide is an antigen derived from a virus, bacterium, fungus, parasite, or can be expressed in a tumor or tumor-associated disease (i.e., cancer), an autoimmune disease, a degenerative disease, a genetic disease, drug addiction, obesity, or an allergic disease.

[0190] In certain embodiments, the heterologous non-arenavirus polypeptide is a viral antigen. Non-limiting examples of viral antigens include Adenoviridae (e.g., mastadenovirus and aviadenovirus), Herpesviridae (e.g., herpes simplex virus type 1, herpes simplex virus type 2, herpes simplex virus type 5, herpes simplex virus type 6, Epstein-Barr virus, HHV6-HHV8, cytomegalovirus, and varicella-zoster virus), Leviviridae (e.g., levivirus, enteric bacteriophage MS2, allorevirus), Orthomyxoviridae (e.g., Influenza A virus, influenza B virus, influenza C virus), Parvoviridae (e.g., parvovirus B19), Filoviridae (e.g., Ebola virus, Marburg virus), Hantaviridae, Poxviridae (e.g., Chordopoxviridae, Parapoxvirus, Avipoxvirus, Capripoxvirus, Leporipoxvirus, Suipoxvirus, Morsipoxvirus, and Entomopoxvirinae), Polio Family: Mycoviridae, Papillomaviridae (e.g., human papillomavirus), Family: Paramyxoviridae (e.g., paramyxoviruses, parainfluenza virus type 1, mobiliviruses (e.g., measles virus), rubulaviruses (e.g., mumps virus)), Family: Pneumoviridae (e.g., pneumoviruses, human respiratory syncytial viruses, and metapneumoviruses (e.g., avian pneumovirus and human metapneumovirus)), Family: Picornaviridae (e.g., enteroviruses, rhinoviruses, hepatoviruses (e.g., human hepatitis A virus), cardioviruses, and aphthoviruses), Family: Reoviridae (e.g., orthoreoviruses, orbiviruses, rotaviruses, cypoviruses, phyziviruses, phytreoviruses, and oryzaviruses), Family: Retroviridae (e.g., mammalian type B retroviruses, mammalian type C retroviruses, avian type C retroviruses, type D retrovirus group, BLV-HTLV retroviruses, lentiviruses (e.g., human immunodeficiency virus (HIV)) 1 and HIV-2 (e.g., HIV gp160), Spumaviruses), Flaviviridae (e.g.,Viruses, such as Hepatitis C virus, Dengue virus, and West Nile virus), Hepadnaviridae (e.g., Hepatitis B virus), Togaviridae (e.g., Alphaviruses (e.g., Sindbis virus) and Rubiviruses (e.g., Rubella virus)), Rhabdoviridae (e.g., Vesiculoviruses, Lyssaviruses, Ephemeloviruses, Cytorhabdoviruses, and Nucleorhabdoviruses), Arenaviridae (e.g., Arenaviruses, Lymphocytic Choriomeningitis virus, Yippee virus, Mobara virus, Mopeia virus, Amapari virus, Flexar virus, Gunarito virus, Junin virus, Latinoviruses, Machupo virus, Oliveros virus, Parana virus, Piquinde virus, Piritar virus, Sabia virus, Tacaribe virus, Tamiami virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuayo virus (ALLV), and Lassa virus), and Coronaviridae (e.g., Coronavirus and Torovirus). In certain embodiments, the arenavirus particles described herein are selected from the group consisting of: Mammarenavirus (e.g., Alpahuayovirus, Arxavirus, Juninvirus, Bear Canyonvirus, Sabiavirus, Piquindevirus, Chaparevirus, Lijiangvirus, Cupixivirus, Flexarvirus, Gairovirus, Ganaritovirus, Yippievirus, Lassavirus, Latinovirus, Loei Rivervirus, Lujovirus, Lunavirus, Lulivirus, Runkuvirus, Lymphocytic choriomeningitisvirus, Machupovirus, Marientalvirus, Merinowalkvirus, , Mobaravirus, Mopeiavirus, Morogorovirus, Okahandjavirus, Oliverosvirus, Paranavirus, Piritarvirus, Aporevirus, Ryukyuvirus, Amaparivirus, Solwezivirus, Thulevirus, Tacaribevirus, Tamiamivirus, Unshu virus, Whitewater Arroyo virus, Big Brushy Tank virus, Catalinavirus, Skinner Tank virus, Tonto River virus, or Shapuli virus), wherein the arenavirus particle contains a genome encoding an antigen from the GP, NP, Z, orand L. In a specific embodiment, the viral antigen is HIV gp120, gp41, HIV Nef, RSV F glycoprotein, RSV G glycoprotein, HTLV tax, herpes simplex virus glycoprotein (e.g., gB, gC, gD, and gE), or hepatitis B surface antigen, hepatitis C virus E protein, or coronavirus spike protein. In one embodiment, the viral antigen is not an HIV antigen.

[0191] In other embodiments, the heterologous non-arenavirus polypeptide is a bacterial antigen (e.g., a bacterial coat protein). Non-limiting examples of bacterial antigens include Aquaspirillaceae, Azospirillaceae, Azotobacteraceae, Bacteroidales, Bartonella spp., Bdellovibrioaceae, Campylobacter spp., Chlamydia spp. (e.g., Chlamydia pneumoniae), Clostridium spp., Enterobacteriaceae (e.g., Citrobacter spp., Edwardsiella spp., Enterobacter aerogenes, Envinia spp., Escherichia coli, Hafnia spp., Klebsiella spp., Morganella spp., Proteus vulgaris, and the like. vulgaris, Providencia, Salmonella spp., Serratia marcescens, and Shigella flexneri), Gardinellaceae, Haemophilus influenzae, Halobacteriaceae, Helicobacteraceae, Legionellaceae, Listeria spp., Methylococcusceae, mycobacteria (e.g., Mycobacterium tuberculosis), tuberculosis), Neisseriaceae, Oceanospirillaceae, Pasteurellaceae, Pneumococcus spp., Pseudomonas spp., Rhizobiumaceae, Spirillaceae, Spirosomaceae, Staphylococcus (e.g., methicillin-resistant Staphylococcus aureus and Staphylococcus pyrogenes), Streptococcus (e.g., Streptococcus enteritidis, Streptococcus fasciae, and Streptococcus pneumoniae),pneumoniae), Vampirovibr Helicobacter, Yersiniaceae, Bacillus anthracis, and Vampirovibrionaceae.

[0192] In other embodiments, the heterologous non-arenavirus polypeptide is a parasite antigen (e.g., a protozoan antigen). Non-limiting examples of parasite antigens include antigens from parasites such as amoeba, malaria parasite, Plasmodium, and Trypanosoma cruzi.

[0193] In yet other embodiments, the heterologous non-arenavirus polypeptide is a fungal antigen. Non-limiting examples of fungal antigens include those from Absidia species (e.g., Absidia corymbifera and Absidia ramosa), Aspergillus species (e.g., Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus), Basidiobolus ranarum, Blastomyces dermatitidis, and the like. dermatitidis, Candida species (e.g., Candida albicans, Candida glabrata, Candida kern, Candida krusei, Candida parapsilosis, Candida pseudotropicalis, Candida quillermondii, Candida rugosa, Candida stellatoidea, and Candida tropicalis), Coccidioides immitis immitis, Conidiobolus species, Cryptococcus neoforms, Cunninghamella species, dermatophytes, Histoplasma capsulatum, Microsporum gypseum, Mucor pusilluspusillus, Paracoccidioides brasiliensis, Pseudallescheria boydii, Rhinosporidium seeberi, Pneumocystis carinii, Rhizopus species (e.g., Rhizopus arrhizus, Rhizopus oryzae, and Rhizopus microsporus), Saccharomyces species, Sporothrix schenckii, schenckii, Zygomycetes, and antigens from fungi of the classes Zygomycetes, Ascomycetes, Basidiomycetes, Deuteromycetes, and Oomycetes.

[0194] In some embodiments, the heterologous non-arenavirus polypeptide is a tumor neoantigen. As used herein, "neoantigen" refers to an antigen that arises due to a mutation in a tumor cell; such antigens are not normally expressed in normal cells or tissues. Without being bound by theory, neoantigens represent preferred targets because healthy tissues do not normally express these antigens. Furthermore, without being bound by theory, in the context of the present invention, T cells that recognize neoantigens may not have undergone negative thymic selection or are functionally unaffected by peripheral tolerance mechanisms. Therefore, such cells have high functional avidity for the antigen and can mount a strong immune response against the tumor while lacking the risk of inducing destruction of normal tissues and autoimmune damage. In certain embodiments, the neoantigen is an MHC class I-restricted neoantigen. In certain embodiments, the neoantigen is an MHC class II-restricted neoantigen. In certain embodiments, mutations in a patient's tumor cells give rise to novel proteins that produce neoantigens. In certain embodiments, the heterologous non-arenavirus polypeptide is a tumor neoepitope. In certain embodiments, the neoepitope is an MHC class I-restricted neoepitope. In certain embodiments, the neoepitope is an MHC class II-restricted neoepitope.

[0195] In some embodiments, the heterologous non-arenavirus polypeptide is a tumor antigen or tumor-associated antigen, such as acute lymphoblastic leukemia, acute myeloid leukemia, adrenocortical carcinoma, childhood adrenocortical carcinoma, AIDS-related cancer, Kaposi's sarcoma, anal cancer, appendiceal cancer, astrocytoma, atypical teratoid / rhabdomyosarcoma, basal cell carcinoma, extrahepatic bile duct carcinoma (see cholangiocarcinoma), bladder cancer, osteosarcoma / malignant fibrous histiocytoma, brain stem glioma, brain tumor, brain tumor, cerebellar astrocytoma, cerebral astrocytoma / malignant glioma brain tumor, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, visual pathway and hypothalamic glioma, breast cancer, bronchial adenoma / carcinoid , Burkitt's lymphoma, carcinoid tumor, carcinoid gastrointestinal tumor, cancer of unknown primary, central nervous system lymphoma, primary cerebellar astrocytoma, cerebral astrocytoma / malignant glioma, cervical cancer, childhood cancer, chronic bronchitis, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorder, colon cancer, cutaneous T-cell lymphoma, desmoplastic small round cell tumor, emphysema, endometrial cancer, ependymoma, esophageal cancer, Ewing's sarcoma in Ewing's family of tumors, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct carcinoma, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric (Stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, germ cell tumor: extracranial, extragonadal, or ovarian gestational trophoblastic tumor, brain stem glioma, glioma, childhood brain astrocytoma, childhood visual pathway and hypothalamus, gastric carcinoid, hairy cell leukemia, head and neck cancer, heart cancer, hepatocellular (liver) cancer, Hodgkin's lymphoma, hypopharyngeal cancer, hypothalamic and visual pathway glioma, intraocular melanoma, islet cell carcinoma (endocrine pancreas), Kaposi's sarcoma, kidney cancer (renal cell carcinoma), laryngeal cancer, acute lymphoblastic lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia Disease, chronic myeloid leukemia, lip and oral cancer, liposarcoma, liver cancer (primary), lung cancer, non-small cell, small cell, AIDS-related lymphoma, Burkitt's lymphoma, cutaneous T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, lymphoma, primary central nervous system, macroglobulinemia, Waldenstrom's, male breast cancer, malignant fibrous histiocytoma / osteosarcoma of bone, medulloblastoma, melanoma, intraocular (eye), Merkel cell carcinoma, mesothelioma, adult malignancies, mesothelioma, metastatic squamous cell neck cancer of unknown primary, oral cancer, multiple endocrine neoplasia syndrome, multiple myeloma / plasma cell neoplasm, mycosis fungoides,Myelodysplastic syndromes, myelodysplastic / myeloproliferative disorders, myeloid leukemia, chronic, myeloid leukemia, adult acute, myeloid leukemia, childhood acute, myeloma, multiple (cancer of the bone marrow), myeloproliferative disorders, chronic, nasal and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, non-small cell lung cancer, oligodendroglioma, oral cancer, oropharyngeal cancer, osteosarcoma / malignant fibrous histiocytoma of bone, ovarian cancer, ovarian epithelial carcinoma (surface epithelial-stromal tumor), ovarian germ cell tumor, ovarian low malignant potential tumor, pancreatic cancer, islet cell, paranasal sinus and nasal cancer, parathyroid cancer, penile cancer , pharyngeal cancer, pheochromocytoma, pineal astrocytoma, pineal germinoma, pineoblastoma, and supratentorial primitive neuroectodermal tumor, pituitary adenoma, plasma cell neoplasia / multiple myeloma, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell carcinoma (kidney cancer), renal pelvis and ureter, transitional cell carcinoma, retinoblastoma, rhabdomyosarcoma, childhood, salivary gland cancer, sarcoma, Ewing family tumor, Kaposi's sarcoma, soft tissue sarcoma, uterine sarcoma, Sezary syndrome, skin cancer (non-melanoma), skin cancer (melanoma) , Merkel cell skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma - see skin cancer (non-melanoma), squamous cell neck cancer of unknown primary site, metastatic, gastric cancer, supratentorial primitive neuroectodermal tumor, T-cell lymphoma, skin - see mycosis fungoides and Sézary syndrome, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, childhood transitional cell carcinoma of the renal pelvis and ureter, gestational trophoblastic tumor, unknown primary site, cancer of unknown primary site in adults, childhood cancer, ureter and renal pelvis, transitional cell carcinoma, kidney cancer, uterine cancer, intrauterine Antigens derived from tumor-related diseases include mesenteric sarcoma, bronchial tumors, central nervous system embryonal tumors; childhood chordoma, colorectal cancer, craniopharyngioma, ependymoblastoma, Langerhans cell histiocytosis, acute lymphoblastic leukemia, acute myeloid leukemia (adult / childhood), small cell lung cancer, medullary epithelioma, oral cancer, papillomatosis, intermediately differentiated pineal parenchymal tumor, pituitary tumor, respiratory tract cancer involving the NUT gene on chromosome 15, spinal cord tumor, thymoma, thyroid cancer, vaginal cancer; vulvar cancer, and Wilms' tumor.

[0196] Non-limiting examples of tumor or tumor-associated antigens include adipophilin, AIM-2, ALDH1A1, BCLX(L), BING-4, CALCA, CD45, CPSF, cyclin D1, DKK1, ENAH (hMena), EpCAM, EphA3, EZH2, FGF5, glypican-3, G250 / MN / CAIX, HER-2 / neu, IDO1, IGF2B3, IL13Rα2, intestinal carboxylesterase, alpha-f Etoprotein, kallikrein 4, KIF20A, lenticin, M-CSF, MCSP, mdm-2, Meloe, MMP-2, MMP-7, MUC1, MUC5AC, p53, PAX5, PBF, PRAME, PSMA, RAGE-1, RGS5, RhoC, RNF43, RU2AS, cernin 1, SOX10, STEAP1, survivin, telomerase, VEGF, or WT1, EGF-R, CEA, CD52, gp 100 proteins, MELANA / MART1, NY-ESO-1, p53, MAGE1, MAGE3 and CDK4, α-actinin-4, ARTC1, BCR-ABL fusion protein (b3a2), B-RAF, CASP-5, CASP-8, β-catenin, Cdc27, CDK4, CDKN2A, CLPP, COA-1, dek-can fusion protein, EFTUD2, elongation factor 2, ETV6-AML1 fusion protein, FLT3-IT D, FN1, GPNMB, LDLR-fucosyltransferase AS fusion protein, NFYC, OGT, OS-9, pml-RARα fusion protein, PRDX5, PTPRK, K-ras, N-ras, RBAF600, SIRT2, SNRPD1, SYT-SSX1 or -SSX2 fusion protein, TGF-betaRII, triosephosphate isomerase, lengusin, M-CSF, MCSP, or mdm-2.

[0197] In some embodiments, the heterologous non-arenavirus polypeptide is a respiratory pathogen antigen. In specific embodiments, the respiratory pathogen is a virus such as RSV, coronavirus, human metapneumovirus, parainfluenza virus, Hendra virus, Nipah virus, adenovirus, rhinovirus, or PRRSV. Non-limiting examples of respiratory virus antigens include respiratory syncytial virus F, G, and M2 proteins, coronavirus (SARS, HuCoV) spike protein (S), human metapneumovirus fusion protein, parainfluenza virus fusion protein and hemagglutinin protein (F, HN), Hendra virus (HeV) and Nipah virus (NiV) attachment glycoproteins (G and F), adenovirus capsid protein, rhinovirus protein, and PRRSV wild-type or modified GP5 and M proteins.

[0198] In specific embodiments, the respiratory pathogen is a bacterium such as Bacillus anthracis, Mycobacterium tuberculosis, Bordetella pertussis, Streptococcus pneumoniae, Yersinia pestis, Staphylococcus aureus, Francisella tularensis, Legionella pneumophila, Chlamydia pneumoniae, Pseudomonas aeruginosa, Neisseria meningitides, and Haemophilus influenzae. Non-limiting examples of respiratory bacterial antigens include Bacillus anthracis protective antigen PA, Mycobacterial antigen 85A and heat shock protein (Hsp65), Bordetella pertussis pertussis toxoid (PT) and filamentous hemagglutinin (FHA), Streptococcus pneumoniae sortase A and surface adhesin A (PsaA), Yersinia pestis F1 and V subunits, and proteins from Staphylococcus aureus, Francisella tularensis, Legionella pneumophila, Chlamydia pneumoniae, Pseudomonas aeruginosa, Neisseria meningitidis, and Haemophilus influenzae.

[0199] In some embodiments, the heterologous non-arenavirus polypeptide is a T-cell epitope. In other embodiments, the heterologous ORF encodes a cytokine or growth factor.

[0200] In other embodiments, the heterologous non-arenavirus polypeptide is an antigen expressed in an autoimmune disease. In more specific embodiments, the autoimmune disease can be type I diabetes, multiple sclerosis, rheumatoid arthritis, lupus erythematosus, and psoriasis. Non-limiting examples of autoimmune disease antigens include Ro60, dsDNA, or RNP.

[0201] In other embodiments, the heterologous non-arenavirus polypeptide is an antigen expressed in allergic diseases. In more specific embodiments, allergic diseases include, but are not limited to, seasonal and perennial rhinoconjunctivitis, asthma, and eczema. Non-limiting examples of allergic antigens include Bet v 1 and Fel d 1.

[0202] 5.4 Nucleotide Sequences Provided Herein In one aspect, provided herein is a nucleotide sequence. In one embodiment, provided herein is a nucleotide sequence comprising a first open reading frame (ORF) and a second ORF, wherein one of the two ORFs is in the sense orientation and the other ORF is in the antisense orientation; wherein the first ORF comprises a nucleotide sequence encoding a functional fragment of a first polypeptide, and the first ORF does not encode a full-length first polypeptide; wherein the second ORF is a) a second polypeptide; or b) a functional fragment of the first polypeptide, and the second ORF does not encode the full-length first polypeptide; or c) a functional fragment of a second polypeptide, and the second ORF does not encode a full-length second polypeptide; or d) Heterologous Non-Arenavirus Polypeptides and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenavirus GP, NP, Z, and L.

[0203] In certain embodiments, the first ORF and the second ORF are separated by an arenavirus intergenic region (IGR), and each ORF is under the control of an arenavirus 3' untranslated region (UTR) or an arenavirus 5' UTR.

[0204] In certain embodiments, the first ORF further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide; wherein said third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein said heterologous non-arenavirus polypeptide and said second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0205] In certain embodiments, the second ORF further comprises a nucleotide sequence encoding a second heterologous non-arenavirus polypeptide or a third polypeptide; wherein said third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; and wherein said heterologous non-arenavirus polypeptide and said second heterologous non-arenavirus polypeptide are the same as or different from each other.

[0206] In certain embodiments, the first ORF is part of a transcription unit that further comprises another ORF, wherein the other ORF and the first ORF are separated by an internal ribosome entry site (IRES). In certain embodiments, the second ORF is part of a transcription unit that further comprises another ORF, wherein the other ORF and the second ORF are separated by an IRES. In certain embodiments, the first ORF and / or the second ORF comprises a nucleotide sequence encoding an arenavirus GP signal peptide or a functional fragment thereof, and the other ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide or an arenavirus NP, Z, or L.

[0207] In certain embodiments, the arenaviruses GP, NP, Z, and L are derived from LCMV, Lassa virus, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Guanarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0208] In certain embodiments, provided herein is a nucleotide sequence comprising an open reading frame (ORF), wherein the ORF comprises: a) a functional fragment of a first polypeptide, and b) a heterologous non-arenavirus polypeptide or a second polypeptide comprising a nucleotide sequence encoding wherein the ORF does not encode a full-length first polypeptide; and wherein the first and second polypeptides are different from each other and are selected from the group consisting of arenaviruses GP, NP, Z, and L that are not derived from Lassa virus. In certain embodiments, the first and second polypeptides are selected from the group consisting of arenaviruses GP, NP, Z, and L of LCMV, Piquinde virus, Oliveros virus, Tamiami virus, Mobara virus, Mopeia virus, Yippee virus, Amapari virus, Flexal virus, Gunarito virus, Latino virus, Machupo virus, Parana virus, Piritar virus, Sabia virus, Tacaribe virus, Bear Canyon virus, Whitewater Arroyo virus, Alpahuay virus (ALLV), Alxa virus, Chapare virus, Lijiang virus, Cupixi virus, Gairo virus, Loei River virus, Lujo virus, Luna virus, Luri virus, Runku virus, Mariental virus, Merinowalk virus, Morogoro virus, Okahandja virus, Apore virus, Ryukyu virus, Solwezi virus, Thule virus, Wenzhou virus, Big Brushy Tank virus, Catarina virus, Skinner Tank virus, Tonto River virus, Shapuli virus, or Junin virus.

[0209] In some embodiments, the ORF is a first ORF, and the nucleotide sequence further comprises a second ORF. In some embodiments, the second ORF comprises a nucleotide sequence encoding a third polypeptide, a functional fragment of the first polypeptide, a functional fragment of a third polypeptide, or a second heterologous non-arenavirus polypeptide; wherein the third polypeptide is different from the first polypeptide and the second polypeptide and is selected from the group consisting of arenavirus GP, NP, Z, and L; wherein one of the two ORFs is in the sense orientation and the other ORF is in the antisense orientation; wherein the second ORF does not encode the full-length first polypeptide; wherein the second ORF does not encode the full-length third polypeptide; and wherein the heterologous non-arenavirus polypeptide and the second heterologous non-arenavirus polypeptide are the same as or different from each other. In some embodiments, the second ORF comprises a nucleotide sequence encoding a functional fragment of the first polypeptide, wherein the functional fragment encoded by the first ORF is different from the functional fragment encoded by the second ORF.

[0210] In certain embodiments, the nucleotide sequence does not further comprise a second ORF.

[0211] In certain embodiments, the nucleotide sequence is an arenavirus genome or antigenome S segment. In certain embodiments, the nucleotide sequence is an arenavirus genome or antigenome L segment.

[0212] In certain embodiments, the first ORF is under the control of the arenavirus 3' UTR and the second ORF is under the control of the arenavirus 5' UTR. In certain embodiments, the first ORF is under the control of the arenavirus 5' UTR and the second ORF is under the control of the arenavirus 3' UTR.

[0213] In certain embodiments, the first ORF comprises a nucleotide sequence encoding an arenavirus GP signal peptide, either alone or fused to a heterologous non-arenavirus polypeptide. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the second ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus polypeptide; wherein the heterologous non-arenavirus polypeptide encoded by the first ORF and the heterologous non-arenavirus polypeptide encoded by the second ORF are the same as or different from each other. In certain embodiments, the first ORF is under the control of an arenavirus 3' UTR and the second ORF is under the control of an arenavirus 5' UTR.

[0214] In certain embodiments, the first ORF comprises a nucleotide sequence encoding a heterologous non-arenavirus signal peptide and arenavirus GP1 and GP2. In certain embodiments, the second ORF comprises a nucleotide sequence encoding NP. In certain embodiments, the first ORF is under the control of an arenavirus 5' UTR and the second ORF is under the control of an arenavirus 3' UTR.

[0215] In certain embodiments, the first polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95 , SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO:96, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:118, SEQ ID NO:125, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:51, SEQ ID NO:58, SEQ ID NO:65, SEQ ID NO:72, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:90, SEQ ID NO:97, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:119, SEQ ID NO:126, SEQ ID NO:133, or SEQ ID NO:140;and the second polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:91, SEQ ID NO:98, SEQ ID NO:105, SEQ ID NO:109, SEQ ID NO:113, SEQ ID NO:120, SEQ ID NO:127, SEQ ID NO:134, SEQ ID NO:49, SEQ ID NO:56, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:77, SEQ ID NO:81, SEQ ID NO:88, SEQ ID NO:95, SEQ ID NO: 102, SEQ ID NO:106, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:124, SEQ ID NO:131, SEQ ID NO:138, SEQ ID NO:50, SEQ ID NO:57, SEQ ID NO:64, SEQ ID NO:71, SEQ ID NO:78, SEQ ID NO:82, SEQ ID NO:89, SEQ ID NO...

Claims

1. An arenavirus particle modified so that an arenavirus ORF is generated into two or more mRNA transcripts, The arenavirus particle, wherein the arenavirus ORF encodes an arenavirus GP signal peptide, arenavirus GP1 and GP2, and the arenavirus GP signal peptide is expressed from a first mRNA transcript and arenavirus GP1 and GP2 are expressed from a second mRNA transcript.

2. The arenavirus particle of claim 1 , wherein at least one of the mRNA transcripts comprises an internal ribosome entry site (IRES).

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