Hepatitis C virus immunogenic compositions and methods of use thereof

Abstract

The present disclosure provides an immunogenic composition comprising one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides.The present disclosure provides a method of inducing an immune response against Hepatitis C virus in an individual, the method comprising administering to the individual an immunogenic composition of the present disclosure.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 324,339, filed March 28, 2022, U.S. Provisional Patent Application No. 63 / 358,332, filed July 5, 2022, and U.S. Provisional Patent Application No. 63 / 397,676, filed August 12, 2022, which are incorporated by reference in their entireties herein.

[0002] Incorporation by Reference of Electronically Submitted Specimens The Sequence Listing is provided herewith as Sequence Listing XML, "UALB-058WO_SEQ_LIST," created on March 26, 2023, and having a size of 255,129 bytes. The contents of the Sequence Listing XML are incorporated herein by reference in their entirety.

[0003] Introduction Hepatitis C virus (HCV) is a blood-borne pathogen that is estimated to infect 150-200 million people worldwide. Infection with HCV can be asymptomatic and sometimes cleared by the patient without medical intervention. However, the majority of patients develop chronic HCV infection, which can lead to liver inflammation, scarring and even liver failure or liver cancer. In the United States alone, over 3 million people have a chronic infection.

[0004] The HCV virion contains a positive-sense, single-stranded RNA genome of approximately 9.5 kb. The genome encodes a single polyprotein of 3,010-3,030 amino acids. The structural proteins consist of a core protein that forms the viral nucleocapsid and two envelope glycoproteins, E1 and E2.

[0005] There is a need in the art for compositions and methods that induce an immune response against HCV. Summary of the Invention

[0006] The present disclosure provides an immunogenic composition comprising one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides.The present disclosure provides a method of inducing an immune response against Hepatitis C virus in an individual, the method comprising administering to the individual an immunogenic composition of the present disclosure. [Brief description of the drawings]

[0007] [Figure 1] Figures 1A-1C provide amino acid sequence alignments of examples of the core-E1-E2 coding regions of HCV genotype 1 viruses, specifically, representative HCV 1A, 1B and 1C genotypes. Genbank database sequences of the coding regions core-E1-E2 were aligned using Geneious software v5.6.4. Amino acid numbering is according to strain NP_671941 (H77). Consensus: SEQ ID NO:1; AVI1a129: SEQ ID NO:2; NP_671491 (H77): SEQ ID NO:3; EU155269: SEQ ID NO:4; EU781810: SEQ ID NO:5; EU781771: SEQ ID NO:6; AB250610: SEQ ID NO:7; EU781752: SEQ ID NO:8; EU781759: SEQ ID NO:9; EF407439: SEQ ID NO:10; EF407427: SEQ ID NO:11; EU362905: SEQ ID NO:11; EF407413: SEQ ID NO:11; EU781808: SEQ ID NO:14; EU78170: SEQ ID NO: 15; AJ238799 (Con1): SEQ ID NO: 16; AAK97744: SEQ ID NO: 17; AF139594: SEQ ID NO: 18; AF176573: SEQ ID NO: 19; BAA19625: SEQ ID NO: 20; BAA25076: SEQ ID NO: 21; BAC54896: SEQ ID NO: 22; BAD91386: SEQ ID NO: 23; BAF46764: SEQ ID NO: 24; BAG30950: SEQ ID NO: 24; CAB41951: SEQ ID NO: 26; AAK95832: SEQ ID NO: 27; AAT69968: SEQ ID NO: 28 and BAA03581: SEQ ID NO: 29.

[0008] [Diagram 2]Figures 2A-2C provide an alignment of amino acid sequences of the core-E1-E2 coding regions of representative HCV 2A and HCV2B subtypes. Genbank database sequences of the coding regions core-E1-E2 were aligned using Geneious software v5.6.4. The amino acid numbering represented is consistent with common HCV strains: D00994 (HC-J6) for HCV 2A; ABO47639 (JFH1) and HPCJ8G-J8 (J8) for HCV2A and HCV2B, respectively. AB047639 (JFH1): SEQ ID NO: 30; AB047645: SEQ ID NO: 31; AF169003: SEQ ID NO: 32; AF169005: SEQ ID NO: 33; AF238482: SEQ ID NO: 34; AY746460: SEQ ID NO: 35; HPCPOLP: SEQ ID NO: 36; NC_009823: SEQ ID NO: 37; HPCJ8G HC-J8: SEQ ID NO: 38; AB030907: SEQ ID NO: 39; AY232730: SEQ ID NO: 40; AY232747: SEQ ID NO: 41 and DQ430817: SEQ ID NO: 42.

[0009] [Diagram 3] 3A-3C provide amino acid sequence alignments of the core-E1-E2 coding regions of representative HCV 3A, 3B and 3K genotypes. Genbank database sequences of coding regions core-E1-E2 were aligned using Geneious software v5.6.4. Consensus: SEQ ID NO: 43; AVI3a177: SEQ ID NO: 44; ADF97232 (S52): SEQ ID NO: 45; YP_0014696: SEQ ID NO: 46; CAA54244: SEQ ID NO: 47; AAC03058: SEQ ID NO: 48; AAY29642: SEQ ID NO: 49; ABD85062: SEQ ID NO: 50; ABD85063: SEQ ID NO: 50; ABD97104: SEQ ID NO: 52; BAA06044: SEQ ID NO: 53; BAA08372: SEQ ID NO: 54 and BAA09890: SEQ ID NO: 55.

[0010] [Figure 4]4A-4B provide the amino acid sequence of the core-E1-E2 coding region of HCV genotype 7a. The amino acid sequence of the coding region core-E1-E2 of genotype 7a (isolate QC69; Genbank: ABN05226.1; SEQ ID NO: 56) is shown according to the numbering scheme of the reference strain, NP_671941 (H77).

[0011] [Diagram 5] FIG. 5 depicts HCV E1 / E2-specific IgG levels in mouse serum after vaccination.

[0012] [Figure 6] FIG. 6 depicts neutralization of HCV psueudo particles using post-vaccination mouse sera.

[0013] [Figure 7] 7A-7B present data showing that E1E2-4TP mixtures adjuvanted with SLA-LSQ or SLA-SE can induce the generation of T cells producing IFN-γ, IL-2 and TNF-α.

[0014] [Figure 8] 8A-8B show the structures of several saponins.

[0015] [Figure 9] FIG. 9 depicts the structures of squalene, miglyol 810, DOPC, Tween 80 and Pluronic F68.

[0016] [Figure 10] FIG. 10 provides the amino acid sequence of the TP fusion polypeptide (SEQ ID NO:57).

[0017] [Figure 11] 11A-11C provide the amino acid sequence of the TP465 polypeptide (SEQ ID NOs:58-60, respectively).

[0018] [Figure 12] FIG. 12 provides the amino acid sequences of example T cell epitope polypeptides ("TPs") (SEQ ID NOs:61-70, respectively).

[0019] [Figure 13] 13A-13B present data showing that E1E2-4TP mixtures adjuvanted with SLA-LSQ or SLA-SE can induce the generation of CD4+ T cells producing IFN-γ, IL-2 and TNF-α when stimulated in vitro with individual TPs.

[0020] [Figure 14] 14A-14B present data showing that E1E2-4TP mixtures adjuvanted with SLA-LSQ or SLA-SE can induce the generation of CD8+ T cells producing IFN-γ, IL-2 and TNF-α when stimulated in vitro with individual TPs.

[0021] definition The term "Hepatitis C virus" ("HCV"), as used herein, refers to any one of several different genotypes and isolates of Hepatitis C virus. Thus, "HCV" also encompasses any of the several genotypes, subtypes or quasi-species of HCV, including, for example, genotypes 1, 2, 3, 4, 5, 6, 7, etc., and subtypes (e.g., 1a, 1b, 2a, 2b, 3a, 4a, 4c, etc.) and quasi-species. Representative HCV genotypes and isolates include HCV-1, H77, J6, Con1, isolate 1, BK, EC1, EC10, HC-J2, HC-J5; HC-J6, HC-J7, HC-J8, HC-JT, HCT18, HCT27, HCV-476, HCV-KF, “Hunan”, “Japanese” , "Taiwan", TH, 1 type, 1a type, H77 type 1b, 1c type, 1d type, 1e type, 1f type, 10 type, 2 type, 2a type, 2b type, 2c type, 2d type, 2f Type 3, type 3a, type 3b, type 3g, type 4, type 4a, type 4c, type 4d, type 4f, type 4h, type 4k, type 5, type 5a, type 6, type 6a and type 7a.

[0022] The terms "individual," "host," "subject," and "patient" are used interchangeably herein and refer to mammals, including, but not limited to, non-human primates (e.g., monkeys), equines (e.g., horses), rodents (e.g., rats, mice), and humans.

[0023] As used herein, the term "isolated" with respect to a polypeptide refers to a polypeptide that is in an environment different from that in which the polypeptide naturally occurs. An isolated polypeptide may be purified. "Purified" means that the compound of interest (e.g., a polypeptide) has been separated from components that naturally accompany it. "Purified" can also be used to refer to a polypeptide that has been separated from components that may accompany it during the production of the polypeptide (e.g., during synthesis in vitro). In some embodiments, a polypeptide (or mixture of polypeptides) is substantially pure when the polypeptide (or mixture of polypeptides) is at least 60% or at least 75% by weight free from organic molecules with which it is naturally associated or with which it is associated during production. In some cases, the polypeptide is 30%-60% pure. In some cases, the polypeptide (or mixture of polypeptides) is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% pure by weight. For example, in some cases, an E1 or E2 polypeptide (or a mixture of E1 and E2 polypeptides, e.g., an E1 / E2 heterodimer) is substantially pure when the E1 or E2 polypeptide (or a mixture of E1 and E2 polypeptides) is at least 60% or at least 75% by weight free from organic molecules with which the polypeptide(s) are naturally associated or produced. In some cases, the E1 or E2 polypeptide (or a mixture of E1 and E2 polypeptides) is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% pure by weight. In some cases, when the composition includes an E2 polypeptide, the E2 polypeptide is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% pure by weight.In some cases, when the composition comprises an E1 / E2 heterodimer complex polypeptide, the E1 / E2 heterodimer complex polypeptide is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% pure by weight. In some cases, when the composition comprises a T cell epitope polypeptide, the T cell epitope polypeptide is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% pure by weight.

[0024] The terms "peptide," "polypeptide," and "protein" are used interchangeably herein and refer to polymeric forms of amino acids of any length, which can include coded and non-coded amino acids, as well as polypeptides having chemically or biochemically modified or derivatized amino acids and modified peptide backbones. The term "polypeptide" includes glycosylated polypeptides.

[0025] The term "heterologous" refers to two components defined by their structure originating from different sources. For example, when "heterologous" is used in the context of a polypeptide, the polypeptide includes an operably linked amino acid sequence that can be derived from one or more different polypeptides, e.g., an amino acid sequence that is not operably linked to the polypeptide in nature. In another example where a composition includes an HCV E1 / E2 heterodimer and a "heterologous" polypeptide, the "heterologous" polypeptide is a polypeptide other than HCV E1 or HCV E2. In another example where a fusion polypeptide includes a) a T cell epitope polypeptide ("TP") and b) a heterologous fusion partner polypeptide, the "heterologous fusion partner polypeptide" is one that is not naturally found associated with the T cell epitope polypeptide. In another example where "heterologous" is used in the context of a nucleic acid or nucleotide sequence, the nucleic acid includes an operably linked nucleotide sequence that is not normally linked in nature. For example, an IRES can be heterologous to the nucleotide sequence encoding the HCV E1 and / or E2 polypeptide, where the IRES is derived from an organism (e.g., a virus) other than HCV.

[0026] A "conservative amino acid substitution" is one in which an amino acid residue is replaced by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, conservative amino acid substitutions do not substantially alter the functional properties of a protein. When two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity or degree of similarity can be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well known to those of skill in the art. See, for example, Pearson (1994) Methods Mol. Biol. 24: 307-331, which is incorporated herein by reference. Examples of groups of amino acids that have side chains with similar chemical properties and therefore constitute conservative amino acid substitution groups include: 1) aliphatic side chain-containing amino acids: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic-hydroxyl side chain-containing amino acids: serine and threonine; 3) amide-containing side chain-containing amino acids: asparagine and glutamine; 4) aromatic side chain-containing amino acids: phenylalanine, tyrosine and tryptophan; 5) basic side chain-containing amino acids: lysine, arginine and histidine; 6) acidic side chain-containing amino acids: aspartic acid and glutamic acid, and 7) sulfur-containing side chain-containing amino acids: cysteine ​​and methionine. Examples of conservative amino acid substitution groups include valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamic acid-aspartic acid and asparagine-glutamine.

[0027] Before the present invention is further described, it is to be understood that the invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the techniques used herein are merely for the purpose of describing particular embodiments, and are not intended to be limiting, as the scope of the present invention is limited only by the appended claims.

[0028] Where a range of values ​​is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit, between the upper and lower limits of that range, unless the context clearly dictates otherwise, and any other stated or intervening values ​​in that stated range, are encompassed within the invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded value in the stated range. Where a stated range includes one or both of the limits, ranges excluding either or both of them are also included herein.

[0029] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.Although any method and material similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred method and material are described herein.All publications described herein are incorporated by reference to disclose and describe the method and / or material in connection with which the publication is cited.

[0030] It should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to an "HCV E1 polypeptide" includes a plurality of such polypeptides, a reference to a "QS21 molecule" includes a reference to one or more QS21 molecules and equivalents thereof known to those of skill in the art, and so forth. It is further noted that the claims may be drafted to exclude any optional element. Thus, this statement is intended to serve as a forerunner of the use of exclusive technical language such as "solely," "only," and the like in connection with the recitation of claim elements or the use of "negative" limitations.

[0031] It is understood that certain features of the invention that are described for clarity in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features of the invention that are described for brevity in the context of a single embodiment may also be provided separately or in any suitable subcombination. All combinations of the embodiments of the invention are specifically embraced by the invention and are disclosed herein as if each and every combination were individually and expressly disclosed herein. Moreover, all subcombinations of the various embodiments and elements thereof are also specifically embraced by the invention and are disclosed herein as if each and every such subcombination were individually and expressly disclosed herein.

[0032] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] The present disclosure provides an immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, and b) a second generation lipid adjuvant (SLA) that is a toll-like receptor 4 (TLR4) agonist, formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin. The present disclosure provides an immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) a hepatitis C virus (HCV) E1 and / or HCV E2 polypeptide, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin. The present disclosure provides a method of inducing an immune response against HCV in an individual, comprising administering to the individual an effective amount of the immunogenic composition of the present disclosure.

[0034] As noted above, in some cases, the immunogenic compositions of the present disclosure include both one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides and an HCV E1 and / or E2 polypeptide. The HCV E1 and / or E2 polypeptides function as humoral elements (i.e., to induce the production of neutralizing antibodies), and the T cell epitope polypeptide(s) (or a fusion polypeptide comprising a T cell epitope polypeptide) act as a humoral component (i.e., to induce the production of neutralizing antibodies) and the T cell epitope polypeptide(s) (or a fusion polypeptide comprising a T cell epitope polypeptide) act as a humoral component (i.e., to induce the production of neutralizing antibodies) and / or an HCV E1 and / or E2 polypeptide ... + and CD8 + The inclusion of an adjuvant containing SLA in the immunogenic composition, in a liposomal composition with saponin, or as a stable emulsion, results in a robust CD4 T cell response. + and CD8 + In particular, the use of an adjuvant containing SLA in a liposomal composition with saponin or as a stable emulsion induced a much more robust CD4 T cell response than when alum-OH / MPLA or AddaAS03 were used as adjuvants. + and CD8 + Induced a T cell response.

[0035] immunogenic composition The present disclosure provides an immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.The present disclosure provides an immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0036] The immunogenic compositions of the present disclosure, when administered to an individual, induce more robust CD4 T cell proliferation and activation than reference immunogenic compositions containing Alum-OH / MPLA or AS03 as adjuvants. + T cell responses and / or more robust CD8 + A reference immunogenic composition can induce a T cell response, and the reference immunogenic composition comprises the same T cell epitope polypeptide or a fusion polypeptide comprising a T cell epitope polypeptide as the immunogenic composition of the present disclosure, or the reference immunogenic composition comprises the same T cell epitope polypeptide or a fusion polypeptide comprising a T cell epitope polypeptide and the same HCV E1 and / or E2 polypeptide as the immunogenic composition of the present disclosure. In other words, for comparison, the reference immunogenic composition differs from the immunogenic composition of the present disclosure only in the adjuvant included.

[0037] In some cases, the immunogenic compositions of the present disclosure may be used to compare the CD4 + At least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold or 25-fold more CD4+ T cell responses to HCV + In some cases, the immunogenic compositions of the present disclosure induce a CD8 T cell response induced using a reference immunogenic composition. + at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater than the CD8 T cell response to HCV + In some cases, the immunogenic compositions of the present disclosure induce a CD4 T cell response induced using a reference immunogenic composition. + T cell responses and CD8 +at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater CD4+ T cell response to HCV + T cell responses and CD8 + Induce T cell responses.

[0038] For example, an immunogenic composition of the present disclosure comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin, can be used to compare the CD4+ expression levels induced using a reference immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) Alum-OH / MPLA. + at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater CD4+ T cell response to HCV + It can induce T cell responses.

[0039] As another example, an immunogenic composition of the present disclosure comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin, can be used to measure the CD8+ antibody titer induced using a reference immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) Alum-OH / MPLA. +at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater than the CD8 T cell response to HCV + It can induce T cell responses.

[0040] As another example, an immunogenic composition of the present disclosure comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin, can be used to measure the CD4+ antibody titer induced using a reference immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) AS03. + at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater CD4+ T cell response to HCV + It can induce T cell responses.

[0041] As another example, an immunogenic composition of the present disclosure comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin, can be used to measure the CD8+ expression levels induced using a reference immunogenic composition comprising a) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, b) an HCV E1 and / or HCV E2 polypeptide, and c) AS03. +at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or 2-fold), at least 2.5-fold, at least 5-fold, at least 10-fold, at least 25-fold, or 25-fold greater than the CD8 T cell response to HCV + It can induce T cell responses.

[0042] Alum-OH / MPLA is an adjuvant that contains a) aluminum hydroxide and b) monophosphoryl lipid A (MPLA). AddaS03™ is an oil-in-water nanoemulsion adjuvant that contains squalene, DL-α-tocopherol and polysorbate 80 (Tween® 80). AS03 is an oil-in-water emulsion that contains squalene, polysorbate 80 and α-tocopherol. A dose of AS03 may contain a) 10.69 mg squalene, b) 11.86 mg DL-α-tocopherol and c) 4.86 mg polysorbate 80.

[0043] Squalene has the following structure: [ka]

[0044] Polysorbate 80 has the following structure: [ka]

[0045] Saponin-containing liposome composition (SLA-liposome composition) As mentioned above, in some cases, the immunogenic composition of the present disclosure comprises SLA in a liposomal composition comprising saponin.See, for example, US 2020 / 0276299.The SLA in a liposomal composition comprising saponin is also referred to herein as "SLA-LSQ".

[0046] In some cases, the saponin is present in the liposome composition at a concentration of about 1 μg per unit dose to about 10 μg per unit dose, or about 1 μg per dose to about 8 μg per unit dose. In some cases, the unit dose is 0.5 mL.

[0047] In some cases, the weight ratio of SLA to saponin is about 2.5 to 1.

[0048] In some cases, the liposomal composition comprising the saponin is complexed with a sterol. In some cases, the weight:weight ratio of the saponin to the sterol is about 1:110 to about 1:200, about 1:110 to 1:150, about 1:120 to about 1:150, or about 1:125. In some cases, the weight:weight ratio of the saponin to the sterol is 1:125. In some cases, the sterol is cholesterol. In some cases, the saponin is QS21 and the sterol is cholesterol.

[0049] The saponin may be present in the formulation at a concentration of about 2 μg per mL to about 8 μg per mL. In some cases, a unit dose of the SLA-liposome composition contains 2 μg to 4 μg of saponin. In some cases, the unit dose is 0.5 mL.

[0050] The SLA may be present in the formulation at a concentration of about 5 μg per unit dose to about 10 μg per unit dose. In some cases, the unit dose is 0.5 mL.

[0051] In some cases, the SLA-liposome composition comprises i) 20 μg / mL SLA, ii) 8 μg / mL QS-21, iii) cholesterol, and iv) dioleoylphosphatidylcholine, where the QS21 and cholesterol are present in a weight:weight (w:w) ratio of 1:125. The dioleoylphosphatidylcholine and cholesterol may be present in a w:w ratio of 4:1.

[0052] Liposomes may have an average diameter (i.e., number average diameter) of 1 micrometer or less. In some cases, the average particle size (i.e., number average diameter) of liposome particles is about 900 nm or less, about 800 nm or less, about 700 nm or less, about 600 nm or less, about 500 nm or less, about 400 nm or less, 300 nm or less, or 200 nm or less, for example, about 50 nm to about 900 nm, about 50 nm to about 800 nm, about 50 nm to about 700 nm, about 50 nm to about 600 nm, about 50 nm to about 500 nm, about 50 nm to about 400 nm, about 50 nm to about 300 nm, about 50 nm to about 200 nm, about 50 nm to about 175 nm, about 50 nm to about 150 nm, about 50 nm to about 125 nm, or about 50 nm to about 100 nm. The size of the liposome is about 80 nm, about 85 nm, about 90 nm, about 95 nm, about 100 nm, about 105 nm, about 110 nm, about 115 nm, about 120 nm, about 125 nm, about 130 nm, about 135 nm, about 140 nm, about 145 nm, about 150 nm, about 155 nm, about 160 nm, about 165 nm, about 170 nm, about 175 nm, about 180 nm, about 185 nm, about 190 nm, about 195 nm, or about 200 nm.

[0053] Phospholipids The SLA-liposome composition may include a phospholipid. Suitable phospholipids include 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-disoleoyl-sn-glycero-3-phosphatidylcholine (DOPC), 1-palmitoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1-palmito ... Toyl, 2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), distearoyltrimethylammoniumpropane (DSTAP), dipalmitoyl (C16:0)trimethylammoniumpropane (DPTAP), 1,2-diostearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (DPPE), 1,2-dimyristoyl- sn-glycero-3-phosphatidylethanolamine (DMPE), 1,2-dilauroyl-sn-glycero-3-phosphorylglycerol (DLPG), 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG), 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG), 1,2-distearoyl-sn-glycero- 3-phosphoglycerol (DOPG), 1,2-dilauroyl-sn-glycero-3-phosphatidylethanolamine (DLPE), 1,2-dilauroyl-sn-glycero-3-phosphatidylserine (DLPS), 1,2-dilauroyl-sn-glycero-3-phospho-L-serine, DMPS: 1,2-myristoyl-sn-glycero-3-phospho-L-serine, DPPS: 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine, DSPS 1,2-distearoyl-sn-glycero-3-phospho-L-serine, DOPS: 1,2-distearoyl-sn-glycero-3-phospho-L-serine, POPS: 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine, DLPI: 1,2-dilauroyl-sn-glycero-3-phospho-(1'-myo-inositol), DMPI: 1,2-myristoyl-sn-glycero-3-phospho-(1'-myo-inositol), DPPI: 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-myo-inositol), DSPI: 1,2-distearoyl-sn-glycero-3-phosphoinositol, DOPI: 1,2-distearoyl-sn-glycero-3-phospho-(1'-myo-inositol) and POPI: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoinositol. In some cases, the phospholipid is selected from DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DLPG, DMPG, DPPG, DSPG, DOPG, DSTAP, DPTAP, DSPE, DPPE, DMPE, and DLPE.

[0054] saponin In some cases, the saponin is an immunologically active saponin fraction from the bark of Quillaja saponaria Molina. In some cases, the saponin is QS21.

[0055] QS21 has the following structure: [ka]

[0056] In some cases, the saponin is a synthetic saponin, such as synthetic QS21 (SQS21), QS21-Api, or QS21-Xyl. See, e.g., Ragupathi et al. (2011) Expert Rev. Vaccines 10:463.

[0057] As shown in FIG. 8A, naturally occurring QS-21 has (i) a triterpene aglycone core, quillic acid, (ii) a branched trisaccharide attached to the C3 OH group of the quillic acid by a beta-glycosidic ether bond, and (iii) a linear tetrasaccharide attached to the C28 carboxyl group of the quillic acid by a beta-glycosidic ester bond. The reducing end of the C28 tetrasaccharide is a β-D-fucosyl unit capped at its 4-O position with a glycosylated pseudodimeric fatty acyl chain. QS-21 is a mixture of two isomeric bidesmosidic saponins. The two structural isomers of QS-21 differ in the non-reducing end of the C28 tetrasaccharide. One isomer, QS-21 api has a terminal β-D-apiosil unit, whereas the other isomer, QS-21 xyl has terminal β-D-xylosyl units.

[0058] In some cases, the saponin includes Quil-A or a derivative thereof, such as QS7. Other suitable saponins include Escin, Digitonin, Gypsophila saponin, or Chenopodium quinoa saponin. In some cases, the saponin includes QS-7. In some cases, the saponin includes QS-17. In some cases, the saponin includes QS-18. The structures of QS-7, QS-17, and QS-18 are depicted in FIG. 8B.

[0059] Stable Emulsion As mentioned above, in some cases, the immunogenic composition of the present disclosure comprises SLA in a stable oil-in-water emulsion ("SE"). SLA in a stable oil-in-water emulsion is also referred to herein as "SLA-SE". US2015 / 0017191.

[0060] In some cases, the SLA-SE is an emulsion comprising a) an aqueous phase comprising i) an ammonium phosphate buffer, ii) a surfactant (e.g., Pluronic F68 or Tween 80) and iii) glycerol, and b) an oil phase comprising i) SLA, ii) a phosphatidylcholine (PC) and iii) squalene. Miglyol 810 can be used in place of squalene. In some cases, the SLA-SE comprises 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as the PC. In some cases, the SLA-SE does not comprise an antioxidant. In some cases, the SLA-SE comprises an antioxidant, for example, the antioxidant is tocopherol (vitamin E). In some cases, the surfactant is Pluronic F68.

[0061] In some cases, squalene is present at a concentration of about 0.01% v / v to about 1% v / v. The hydrophobic:lipophilic balance of the emulsion is generally greater than about 9 (e.g., greater than 10, or between 9 and 12). In some cases, squalene is present at a concentration of about 0.01% v / v to 0.5% v / v. In some cases, the emulsion includes 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as the PC. In some cases, the emulsion includes DOPC as the PC.

[0062] The PC can be egg yolk PC, soybean PC, 1,2-disoleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine or 1,2-diarachidonoyl-sn-glycero-3-phosphocholine. In some cases, the PC is DOPC.

[0063] The structures of squalene, Miglyol 810, DOPC, Tween 80 and Pluronic F68 are depicted in FIG.

[0064] In some cases, the SLA-SE comprises i) 10% wt / vol squalene, ii) 0.25 mg / mL SLA, iii) 0.5% wt / vol Vitamin E, iv) glycerol, and v) PC.

[0065] In some cases, the SLA-SE includes the components shown in the table below. [Table 1]

[0066] TLR7 / 8 agonists The present disclosure provides immunogenic compositions comprising a) a toll-like receptor (TLR) 7 / 8 agonist and b) one or more T cell epitope polypeptides (one or more "TPs"). The present disclosure provides immunogenic compositions comprising a) a TLR 7 / 8 agonist and b) a fusion polypeptide comprising two or more TPs. The present disclosure provides immunogenic compositions comprising a) a TLR 7 / 8 agonist, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present disclosure provides immunogenic compositions comprising a) a TLR 7 / 8 agonist, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0067] In some cases, the TLR 7 / 8 agonist is 3M-052 (also called "Telratolimod" or "MEDI9197"). The 3M-052 adjuvant is an imidazoquinoline with an 18-C fatty acyl chain, which confers enhanced hydrophobicity, reduced systemic dissemination and improved bioavailability. In some cases, the 3M-052 is formulated with poly(lactic-co-glycolic acid) (PLGA). In some cases, the 3M-052 is formulated with PLGA nanoparticles. In some cases, the 3M-052 is formulated with alum.

[0068] 3M-052 has the following structure: [ka]

[0069] Additional adjuvants The present disclosure provides immunogenic compositions comprising a) one or more adjuvants and b) one or more T cell epitope polypeptides (one or more "TPs"). The present disclosure provides immunogenic compositions comprising a) one or more adjuvants and b) a fusion polypeptide comprising two or more TPs. The present disclosure provides immunogenic compositions comprising a) one or more adjuvants, b) one or more TPs and c) an HCV E1 polypeptide, an HCV E2 polypeptide or an HCV E1 / E2 heterodimer. The present disclosure provides immunogenic compositions comprising a) one or more adjuvants, b) a fusion polypeptide comprising two or more TPs and c) an HCV E1 polypeptide, an HCV E2 polypeptide or an HCV E1 / E2 heterodimer. The one or more adjuvants may be one or more of those listed below. In some cases, the one or more adjuvants include a combination of those listed above (e.g., SLA-SE or SLA-LSQ) and one or more of those listed below.

[0070] Suitable adjuvants include, for example, monophosphoryl lipid A (MPL), 3-Q-desacyl-4'-monophosphoryl lipid A (3DMPL), poly(D,L-lactide-co-glycolide) (PLG), 3M-052, MF59, AS03, AS04, AS01, CpG-containing nucleic acid (cytosine unmethylated), aluminum phosphate, aluminum hydroxide, alum, and combinations thereof. MF59 is 4.3% w / v squalene, 0.5% w / v Tween 80™, 0.5% w / v Span 85. In some cases, the adjuvant is aluminum hydroxide. In some cases, the adjuvant is alum+MPL. In some cases, the adjuvant is MF59. In some cases, the adjuvant is alum+MF59. In some cases, the adjuvant is AS01. AS01 contains QS-21 Stimulon® adjuvant, MPL and liposomes. In some cases, the adjuvant contains QS21 and MPL in a liposomal formulation. In some cases, the adjuvant is AS03. A dose of AS03 contains 10.69 mg squalene, 11.86 mg DL-α-tocopherol and 4.86 mg polysorbate-80. In some cases, the adjuvant contains aluminum hydroxide and MPL. In some cases, the adjuvant is AS04. AS04 contains aluminum hydroxide and MPL. In some cases, the adjuvant is AS15. AS15 is a combination of QS-21 Stimulon® adjuvant, monophosphoryl lipid A and CpG7909 (oligonucleotide of sequence 5'-TCGTCGTTTTGTCGTTTTGTCGTT-3'; (SEQ ID NO: 71)) in a liposomal formulation. In some examples, the adjuvant is a cyclic dinucleotide (CDN). In some instances, the adjuvant is CpG 1018 (an oligonucleotide of the sequence: 5'TGACTGTGAACGTTCGAGATGA3' (SEQ ID NO: 72)).

[0071] In some cases, a CDN suitable for use in the immunogenic compositions of the present disclosure belongs to formula (I): [ka]

[0072] During the ceremony,

[0073] A is S or O;

[0074] X is S, N, O, or CH2;

[0075] Y, Y' are NH, CH, O;

[0076] Z, Z' are NH, CH2, O;

[0077] R1 represents hydrogen or optionally substituted NH2;

[0078] R2 is hydrogen or absent;

[0079] R3 represents NH2, O, OH, H or a halogen;

[0080] R4 represents hydrogen, halogen, or an optionally substituted linear or branched C1-C6 alkyl group;

[0081] R5 represents hydrogen, OH or a linear or branched C1-C6 alkyl chain or an optionally substituted C1-C6 linear or branched alkoxy;

[0082] TIFF2025510657000008.tif16157 is a single or double bond;

[0083] or a conjugate thereof, and a salt thereof, or a solvate thereof. See, e.g., US2008 / 0286296.

[0084] In formula (I), the purine residue is in some cases guanine (G), adenine (A), xanthine or hypoxanthine (X) or inosine (I) residue. The compound may have the same purine residue, for example, c-diGMP, c-diAMP, c-diIMP or c-dXMP, or may contain different purine residues, for example, c-GpAp, c-GpIp, c-GpXp, c-ApIp, c-ApXp or c-IpXp. Furthermore, R5 is in some cases an OH group. Furthermore, X is in some cases an oxygen atom. In one embodiment, Y, Y', Z and Z' are oxygen atoms, O. Thus, in one embodiment, the compound of formula (I) is cyclic bis(3'-5')diguanylic acid (c-diGMP) or a conjugate thereof or cyclic bis(3'-5')diadenylic acid (c-diAMP) or a conjugate thereof or a salt thereof or a solvate thereof. In one embodiment, the compound of formula (I) is cyclic bis(3'-5')adenylic acid, also called c-di-AMP, or a pegylated conjugate. "Optionally substituted" means substitution with linear or branched C1-C6 alkyl groups or linear or branched C1-C6 alkoxy groups and / or with halogen, hydroxyl or carboxyl groups.

[0085] In some cases, the CDN suitable for use in the immunogenic composition of the present disclosure is selected from the group consisting of cyclic diadenosine monophosphate (c-di-AMP), cyclic diguanosine monophosphate (c-di-GMP) and cyclic GMP-adenosine monophosphate (cGAMP). In some cases, the CDN suitable for use in the immunogenic composition of the present disclosure is cGAMP (2'-3'-cyclic GMP-AMP) or cGAMP (3'-3'-cyclic GMP-AMP). In some cases, the CDN suitable for use in the immunogenic composition of the present disclosure is cGAMP (2'-3'-cyclic GMP-AMP). In some cases, the CDN suitable for use in the immunogenic composition of the present disclosure is cGAMP (3'-3'-cyclic GMP-AMP).

[0086] In some cases, a CDN suitable for use in the immunogenic compositions of the present disclosure belongs to formula (II): [ka]

[0087] During the ceremony,

[0088] A, C, A' and C' are independently selected from NH, O and S;

[0089] X, Y, X' and Y' are independently selected from O or S;

[0090] Z and Z' are independently selected from O, S, NH and CH2;

[0091] B1 and B2 are independently [ka]

[0092] During the ceremony,

[0093] Q is hydrogen or NH2;

[0094] the nitrogen is optionally substituted with a C1-C6 alkyl or C1-C6 acyl group;

[0095] R is O or S is a purine selected from

[0096] In some cases, a CDN suitable for inclusion in the immunogenic composition of the present disclosure is a fluorinated CDN. In some cases, the fluorinated CDN has the following structure: [ka] The 2'-Fc-diGMP has the structure:

[0097] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-SE adjuvant and a cyclic dinucleotide (CDN) as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CDN as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CDN as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CDN as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0098] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-LSQ adjuvant and a CDN as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and a CDN as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and a CDN as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and a CDN as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0099] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-SE adjuvant and 3M-052 as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and 3M-052 as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and 3M-052 as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and 3M-052 as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0100] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-LSQ adjuvant and 3M-052 as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and 3M-052 as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and 3M-052 as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and 3M-052 as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0101] In some cases, the immunogenic composition of the present disclosure comprises a) an SLA-SE adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, and b) one or more TPs. The present disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, and b) a fusion polypeptide comprising two or more TPs. The present disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0102] In some cases, the immunogenic compositions of the disclosure include a) an SLA-LSQ adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, and b) one or more TPs. The disclosure provides immunogenic compositions that include a) an SLA-LSQ adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, and b) a fusion polypeptide that includes two or more TPs. The disclosure provides immunogenic compositions that include a) an SLA-LSQ adjuvant and a CpG oligonucleotide (e.g., CpG 1018) as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present disclosure provides immunogenic compositions comprising: a) an SLA-LSQ adjuvant as described above and a CpG oligonucleotide (e.g., CpG 1018); b) a fusion polypeptide comprising two or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0103] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-SE adjuvant and AS03 as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and AS03 as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and AS03 as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-SE adjuvant and AS03 as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0104] In some cases, the immunogenic composition of the disclosure comprises a) an SLA-LSQ adjuvant and AS03 as described above, and b) one or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and AS03 as described above, and b) a fusion polypeptide comprising two or more TPs. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and AS03 as described above, b) one or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The disclosure provides an immunogenic composition comprising a) an SLA-LSQ adjuvant and AS03 as described above, b) a fusion polypeptide comprising two or more TPs, and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0105] Compositions Comprising T Cell Epitope Polypeptides As noted above, the immunogenic compositions of the present disclosure comprise a) one or more T cell epitope polypeptides (also referred to herein as "TPs") or b) a fusion polypeptide comprising two or more TPs.

[0106] Suitable TPs include i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide and xxiv) a TP1987 polypeptide.

[0107] Suitable TPs include the TP35-NS3, TP50C, TP27, TP48, TP65 and TP240 polypeptides as described below. Suitable TPs include the TP35-NS3, TP50C, TP27, TP48, TP65, TP240, TP156 and TP465 polypeptides as described below.

[0108] In some cases, the TP is derived from an HCV of genotype 1. In some cases, the TP is derived from an HCV of genotype 1a. In some cases, the TP is derived from an HCV of genotype 1b. In some cases, the TP is derived from an HCV of genotype 2. In some cases, the TP is derived from an HCV of genotype 2a. In some cases, the TP is derived from an HCV of genotype 2b. In some cases, the TP is derived from an HCV of genotype 3. In some cases, the TP is derived from an HCV of genotype 3a. In some cases, the TP is derived from an HCV of genotype 4. In some cases, the TP is derived from an HCV of genotype 5. In some cases, the TP is derived from an HCV of genotype 6. In some cases, the TP is derived from an HCV of genotype 7. In some cases, the compositions of the present disclosure include TPs of two or more different genotypes of HCV.

[0109] TP35-NS3 Polypeptide In some instances, the TP35-NS3 T cell epitope polypeptide ("TP35-NS3 polypeptide") comprises the amino acid sequence: KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), where X1 is A or V, X2 is A or V, X3 is A or S, X4 is K or N, X5 is A or S, X6 is Y or F, X7 is M or L, and X8 is K or R, and the TP35-NS3 T cell epitope polypeptide has a length of 35 amino acids to 40 amino acids (e.g., 35, 36, 37, 38, 39, or 40 amino acids). In some instances, the TP35-NS3 polypeptide has a length of 35 amino acids.

[0110] Non-limiting examples of TP35-NS3 polypeptides include i) KSTKVPVAYAAQGYKVLVLNPSVAATLGFGAYLSK (SEQ ID NO: 74), ii) KSTKVPAAYASQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 75), iii) KSTKVPAAYVAQGYNVLVLNPSVAATLGFGSFMSR (SEQ ID NO: 76), iv) KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSR (SEQ ID NO: 77), v) KSTKVPAAYASQGYKVLVLNPSVAATLGFGSYMSK (SEQ ID NO: 78), and vi) KSTKVPAAYASQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 75).

[0111] In some cases, the TP35-NS3 polypeptide comprises an amino acid sequence having at least 80% (at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the amino acid sequence KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79), and the TP35-NS3 polypeptide has a length of 35 amino acids to 40 amino acids (e.g., 35, 36, 37, 38, 39 or 40 amino acids). In some cases, the TP35-NS3 polypeptide comprises the amino acid sequence KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79) and has a length of 35 amino acids.

[0112] TP50C Polypeptide In some instances, the TP50C T cell epitope polypeptide ("TP50C polypeptide") has the amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13PGYP (SEQ ID NO: 80), where X1 is L or V, X2 is A or G, X3 is T or S, X4 is P or R, X5 is A or D, X6 is R or A, X7 is R, Q or S, X8 is S or P, X9 is E, T or Q, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 is Q or K), and the TP50C T cell epitope polypeptide has a length of 50 amino acids to 60 amino acids (e.g., 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 amino acids). In some cases, the TP50C T cell epitope polypeptide has a length of 50 amino acids.

[0113] In some instances, the TP50-C T cell epitope polypeptide has the following amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), where X1 is L or V, X2 is A, X3 is T, X4 is P, X5 is A or D, X6 is R, X7 is R or Q, X8 is S or P, X9 is E or T, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 is Q or K), and the TP50C T cell epitope polypeptide has a length of 50 amino acids to 60 amino acids (e.g., 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 amino acids). In some cases, the TP50C T cell epitope polypeptide has a length of 50 amino acids.

[0114] Non-limiting examples of TP50C polypeptides include i) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYP (SEQ ID NO: 81); ii) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKDRRSTGKSWGKPGYP (SEQ ID NO: 82); iii) GVYVLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 83); iv) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPTGRSWGQPGYP (SEQ ID NO: 84); v) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPTGRHWAQPGYP (SEQ ID NO: 85); and vi) GVYLLPRRGPRLGVRTTRKSSERSQPRGRRQRIPKAASSQGKAWGKPGYP (SEQ ID NO: 86).

[0115] In some cases, the TP50C polypeptide comprises an amino acid sequence having at least 80% (at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87), and the TP50C T cell epitope polypeptide has a length of 50 amino acids to 60 amino acids (e.g., 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 amino acids). In some cases, the TP50C polypeptide comprises the amino acid sequence GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87) and has a length of 50 amino acids.

[0116] TP23 Polypeptide In some cases, the TP23 polypeptide comprises an amino acid sequence having at least 20% (e.g., at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%) amino acid sequence identity to the following amino acid sequence: DVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 88; also referred to herein as "TP23"), and the TP has a length of 18 amino acids to 23 amino acids (e.g., the TP has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa, or 23 aa). In some cases, the TP has a length of 23 amino acids.

[0117] In some instances, the TP23 polypeptide comprises the following amino acid sequence: DVVVX1X2TDALMTGX3TGDFDSVID (SEQ ID NO:89), where X1 is V or C, X2 is A or S, and X3 is F or Y, and the TP23 T cell epitope polypeptide has a length of 18 amino acids to 23 amino acids (e.g., TP has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa, or 23 aa). In some instances, TP has a length of 23 amino acids.

[0118] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVVATDALMTGYTGDFDSVID (SEQ ID NO: 90), and the TP23 polypeptide has a length of 18 amino acids to 23 amino acids (e.g., TP has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa or 23 aa). In some cases, TP has a length of 23 amino acids. In some cases, TP is part of a fusion polypeptide as described in more detail below.

[0119] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCATDALMTGFTGDFDSVID (SEQ ID NO: 91), and the TP23 T cell epitope polypeptide has a length of 18 amino acids to 23 amino acids (e.g., the T cell epitope polypeptide has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa or 23 aa). In some cases, the TP has a length of 23 amino acids. In some cases, the TP is part of a fusion polypeptide as described in more detail below.

[0120] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCSTDALMTGFTGDFDSVID (SEQ ID NO: 92), and the TP23 polypeptide has a length of 18 amino acids to 23 amino acids (e.g., the TP has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa or 23 aa). In some cases, the TP has a length of 23 amino acids. In some cases, the TP is part of a fusion polypeptide as described in more detail below.

[0121] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCATDALMTGYTGDFDSVID (SEQ ID NO: 93), and the TP23 T cell epitope polypeptide has a length of 18 amino acids to 23 amino acids (e.g., the T cell epitope polypeptide has a length of 18 amino acids (aa), 19 aa, 20 aa, 21 aa, 22 aa or 23 aa). In some cases, the TP23 T cell epitope polypeptide has a length of 23 amino acids. In some cases, the TP23 T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0122] In some cases, the TP23 polypeptide comprises an amino acid sequence having at least 20% (e.g., at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the following amino acid sequence: DVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 88; "TP23"), and the TP23 polypeptide has a length of 23 amino acids to 30 amino acids (e.g., a T cell epitope polypeptide has a length of 23 amino acids (aa), 24 aa, 25 aa, 26 aa, 27 aa, 28 aa, 29 aa or 30 aa).

[0123] In some cases, the TP23 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: DVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 88) and has a length of 23 amino acids. In some cases, the TP23 polypeptide comprises the amino acid sequence DVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 88) and has a length of 23 amino acids.

[0124] TP27 Polypeptide In some instances, a TP27 T cell epitope polypeptide ("TP27 polypeptide") comprises the following amino acid sequence: X1X2X3X4KGGRHLIFCHSKKKCDEX5AX6X7LX8 (SEQ ID NO:94), where X1 is L or I, X2 is E, A, S, V or Q, X3 is Q, T, Y, F or L, X4 is I or L, X5 is L or I, X6 is A, K or S, X7 is K, Q or A, and X8 is T, R or S, and the TP27 T cell epitope polypeptide has a length of 27 amino acids to 32 amino acids (e.g., 27, 28, 29, 30, 31 or 32 amino acids). In some instances, the TP27 polypeptide has a length of 27 amino acids.

[0125] Non-limiting examples of TP27 polypeptides include i) LEVIKGGRHLIFCHSKKKCDELAAKLV (SEQ ID NO: 95), ii) IETIKGGRHLIFCHSKKKCDELAAKLS (SEQ ID NO: 96), iii) LSYIKGGRHLIFCHSKKKCDELAAALR (SEQ ID NO: 97), iv) LAFIKGGRHLIFCHSKKKCDELAALR (SEQ ID NO: 98), v) IAQLKGGRHLIFCHSKKKCDEIASKLR (SEQ ID NO: 99), vi) LELIKGGRHLIFCHSKKKCDELAQLT (SEQ ID NO: 100), vii) LEYIKGGRHLIFCHSKKKCDELAKQLT (SEQ ID NO: 101), viii) LQHIKGGRHLIFCHSKKKCDELAGKLT (SEQ ID NO: 102) and ix) LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103).

[0126] In some cases, the TP27 polypeptide comprises an amino acid sequence having at least 80% (at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103), and the TP27 polypeptide has a length of 27 amino acids to 32 amino acids (e.g., 27, 28, 29, 30, 31 or 32 amino acids). In some cases, the TP27 polypeptide has a length of 27 amino acids. In some cases, the TP27 polypeptide comprises the amino acid sequence LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103) and has a length of 27 amino acids.

[0127] TP35-NS4 Polypeptide In some instances, the TP35-NS4 polypeptide has a similar sequence to the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104; also referred to herein as "TP35-NS4") at least 20% (e.g., at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least The T cell epitope polypeptide comprises an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% amino acid sequence identity to the T cell epitope polypeptide, and the T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa or 35 aa). In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0128] In some instances, the TP35-NS4 polypeptide has the following amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 (SEQ ID NO: 105) (wherein X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0129] In some instances, the TP35-NS4 polypeptide has the following amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 (SEQ ID NO: 105) (wherein X1 is I or V, X2 is L, X3 is R, X4 is V or I, X5 is P or Q, X6 is G or A, X7 is A, X8 is V or T, X9 is S or A, and X 10is V), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0130] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYV (SEQ ID NO: 106), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0131] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGQGEGAVQWMNRLIAFASRGNHVAPTHYV (SEQ ID NO: 107), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0132] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: VLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 108), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0133] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGPAEGATQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 109), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0134] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: IIKRHTGTSEGVTQWMNRLIAFASRGNHVSPTHYI (SEQ ID NO: 110), and the TP35-NS4 T cell epitope polypeptide has a length of 28 amino acids to 35 amino acids (e.g., the T cell epitope polypeptide has a length of 28 amino acids (aa), 29 aa, 30 aa, 31 aa, 32 aa, 33 aa, 34 aa, or 35 aa). In some cases, the TP35-NS4 T cell epitope polypeptide has a length of 35 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0135] In some cases, the TP35-NS4 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104), and has a length of 35 amino acids to 40 amino acids (e.g., 35 amino acids (aa), 36 aa, 37 aa, 38 aa, 39 aa, or 40 aa).

[0136] In some cases, the TP35-NS4 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104), and has a length of 35 amino acids. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the present disclosure comprises the amino acid sequence ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104) and has a length of 35 amino acids.

[0137] TP42 Polypeptide In some cases, the TP42 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 111), and has a length of 33 amino acids to about 50 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, 42 aa, or 42 aa to 50 aa). In some cases, the TP42 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 111) and has a length of 42 amino acids. In some cases, the TP42 polypeptide comprises the amino acid sequence GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 111) and has a length of 42 amino acids.

[0138] In some instances, the TP42 polypeptide has the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX 12 X 13(K)n (SEQ ID NO: 112) (wherein X1 is G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R or S, and X 13 is G or S, and n is an integer between 2 and 10), and the TP42 T cell epitope polypeptide has a length of 34 amino acids to 52 amino acids (e.g., 34 amino acids (aa), 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, 42 aa, 43 aa, 44 aa, 45 aa, 46 aa, 47 aa, 48 aa, 49 aa, 50 aa, 51 aa, or 52 aa). In some cases, a TP42 T cell epitope polypeptide suitable for inclusion in a composition of the present disclosure has the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX. 10 X 11 LX 12 X 13 KKK (SEQ ID NO: 112), where X1 is G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R or S, and X 13 is G or S. In some instances, the TP42 polypeptide comprises the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX12 X 13 (K)n (SEQ ID NO: 112) (wherein G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F, V or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R, V or S, and X 13 is G or S, and n is an integer between 2 and 10, and the TP42 T cell epitope polypeptide has a length of 34 amino acids to 52 amino acids (e.g., 34 amino acids (aa), 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, 42 aa, 43 aa, 44 aa, 45 aa, 46 aa, 47 aa, 48 aa, 49 aa, 50 aa, 51 aa, or 52 aa). In some cases, the TP42 polypeptide has the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX. 10 X 11 LX 12 X 13 KKK (SEQ ID NO: 112), where X1 is G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F, V or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R, V or S, and X 13is G or S. In some cases, the TP42 T cell epitope polypeptide has a length of 45 amino acids. In some cases, the TP42 T cell epitope polypeptide has the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTGKKK (SEQ ID NO: 114) and has a length of 45 amino acids.

[0139] In some instances, the TP42 polypeptide has the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX 12 X 13 (SEQ ID NO: 112) (wherein X1 is G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R or S, and X 13 is G or S), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0140] In some cases, the TP42 polypeptide comprises the following amino acid sequence: STTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVA (SEQ ID NO: 115), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0141] In some cases, the TP42 polypeptide comprises the following amino acid sequence: SNTGEIPFYGKAIPIETIKGGRHLIFCHSKKKCDELAAKLSG (SEQ ID NO: 116), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0142] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GQEGEIPFYGRAIPLSYIKGGRHLIFCHSKKKCDELAAALRG (SEQ ID NO: 117), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0143] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GHEGEIPFYGKAIPLAFIKGGRHLIFCHSKKKCDELAALRG (SEQ ID NO: 118), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0144] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GSEGEIPFYGKAIPIAQLKGGRHLIFCHSKKKCDEIASKLRG (SEQ ID NO: 119), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0145] In some cases, a TP42 T cell epitope polypeptide suitable for inclusion in a composition of the present disclosure comprises the following amino acid sequence: PTGEIPFYGKAIPLELIKGGRHLIFCHSKKKCDELAQLTS (SEQ ID NO: 120), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0146] In some cases, the TP42 polypeptide comprises the following amino acid sequence: PSEGEIPFYGRAIPLXLIKGGRHLIFCHSKKKCDELAKQLTS (SEQ ID NO: 121), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0147] In some cases, the TP42 polypeptide comprises the following amino acid sequence: PTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAKQLTS (SEQ ID NO: 122), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the TP42 polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0148] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GNDGEIPFYGKAIPLQHIKGGRHLIFCHSKKKCDELAGKLTS (SEQ ID NO: 123), and the TP42 T cell epitope polypeptide has a length of 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, 37 aa, 38 aa, 39 aa, 40 aa, 41 aa, or 42 aa). In some cases, the TP42 T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide has a length of 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0149] In some cases, a suitable T cell epitope polypeptide is a TP42 polypeptide with one to five amino acids removed from the N-terminus and / or one to five amino acids removed from the C-terminus. Thus, for example, a suitable T cell epitope polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the following amino acid sequence: IPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 124) and has a length of 37 amino acids. As another example, a suitable T cell epitope polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELA (SEQ ID NO: 125), and has a length of 37 amino acids.

[0150] TP45 Polypeptides In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the disclosure comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNV (SEQ ID NO: 127), and has a length of between 45 amino acids and about 50 amino acids. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the present disclosure comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNV (SEQ ID NO: 127), and has a length of 45 amino acids. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the present disclosure comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNV (SEQ ID NO: 127), and has a length of 45 amino acids. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the disclosure comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDKKK (SEQ ID NO: 128) and has a length of 45 amino acids.

[0151] In some instances, the TP45 polypeptide has the following amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10TDALMTGX 11 TGDFDSVIDX 12 X 13 X 14 (K)n (SEQ ID NO: 129) (wherein X1 is L or V, X2 is N or T, X3 is Y or F, X4 is L or V, X5 is S or A, X6 is V or I, X7 is T or A, X8 is S, Q or T, X9 is V or C, and X 10 is A or S, and X 11 is F or Y, and X 12 is C or K, and X 13 is N or K, and X 14 is V or K, and n is an integer from 2 to 10, and the TP45 T cell epitope polypeptide has a length of 36 amino acids to 55 amino acids. In some cases, the TP45 polypeptide has the following amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 11 TGDFDSVIDX 12 X 13 X 14 KKK (SEQ ID NO: 129), where X1 is L or V, X2 is N or T, X3 is Y or F, X4 is L or V, X5 is S or A, X6 is V or I, X7 is T or A, X8 is S, Q or T, X9 is V or C, and X 10 is A or S, and X 11 is F or Y, and X 12 is C or K, and X 13 is N or K, and X 14 is V or K), and the TP45 T cell epitope polypeptide has a length of 48 amino acids. In some cases, the TP45 T cell epitope polypeptide comprises the following amino acid sequence: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNVKKK (SEQ ID NO: 131), and has a length of 48 amino acids.

[0152] In some instances, the TP45 polypeptide has the following amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 11 TGDFDSVIDX 12 X 13 X 14 (SEQ ID NO: 129) (wherein X1 is L or V, X2 is N or T, X3 is Y or F, X4 is L or V, X5 is S or A, X6 is V or I, X7 is T or A, X8 is S, Q or T, X9 is V or C, and X 10 is A or S, and X 11 is F or Y, and X 12 is C or K, and X 13 is N or K, and X 14 is V or K), and the TP45 T cell epitope polypeptide has a length of 36 amino acids to 55 amino acids. In some cases, the TP45 T cell epitope polypeptide has a length of 45 amino acids. In some cases, the TP45 T cell epitope polypeptide is part of a fusion polypeptide, as described in more detail below.

[0153] In some instances, the TP45 polypeptide has the following amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 11 TGDFDSVIDX 12 X 13 X 14 (SEQ ID NO: 129) (wherein X1 is L, X2 is N, X3 is Y, X4 is L, X5 is S, X6 is V, X7 is T, X8 is S, Q or T, X9 is V or C, and X 10 is A and X 11 is F or Y, and X 12 is K and X 13 is K and X 14is K), and the TP45 T cell epitope polypeptide has a length of 36 amino acids to 55 amino acids. In some cases, the TP45 T cell epitope polypeptide has a length of 45 amino acids.

[0154] In some instances, a suitable T cell epitope polypeptide is a TP45 polypeptide having between 1 and 5 amino acids removed from the N-terminus and / or between 1 and 5 amino acids removed from the C-terminus. Thus, for example, in some instances, a TP45 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 133), and has a length of 43 amino acids. For example, in some instances, the TP45 polypeptide comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 133) and has a length of 43 amino acids.

[0155] TP48 Polypeptide In some instances, the TP48 T cell epitope polypeptide ("TP48 polypeptide") has the following amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I, and X 11 is P, T, A or Q, and X 12 is E or D, and X 13 is S, T or D, and X 14 is S or A, and X 15 is A, Q, R or K, and X 16 is R, K or X, and X 17 is T or M, and X 18 is Q, A, T or G, and X 19 is I, L, or V), and the TP48 T cell epitope polypeptide has a length of 48 amino acids to 53 amino acids (e.g., 48, 49, 50, 51, 52, or 53 amino acids). In some cases, the TP48 polypeptide has a length of 48 amino acids.

[0156] Non-limiting examples of TP48 polypeptides include: i) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAIL (SEQ ID NO: 135); ii) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136); iii) ILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYVTESDASQRVTQLL (SEQ ID NO: 137); iv) ILRRHVGQGEGAVQWMNRLIAFASRGNHVAPTHYVAESDASQRVTQVL (SEQ ID NO: 138); vi) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTALL (SEQ ID NO: 139), vii) VLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYVPETDASAKVTQLL (SEQ ID NO: 140), viii) IIKRHTGTSEGVTQWMNRLIAFASRGNHVSPTHYIQDDDASKRVMGIL (SEQ ID NO: 141) and ix) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136).

[0157] In some cases, the TP48 polypeptide comprises an amino acid sequence having at least 80% (at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), and the TP48 T cell epitope polypeptide has a length of 48 amino acids to 53 amino acids (e.g., 48, 49, 50, 51, 52 or 53 amino acids). In some cases, the TP48 polypeptide has a length of 48 amino acids. In some cases, the TP48 polypeptide comprises the amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136) and has a length of 48 amino acids.

[0158] TP33 Polypeptide In some instances, the TP33 polypeptide has a sequence similar to or similar to the following amino acid sequence: HSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 142), at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity, and having a length of 33 amino acids to about 37 amino acids (e.g., having a length of 33 amino acids (aa), 34 aa, 35 aa, 36 aa or 37 aa), or having a length of 30 amino acids to about 33 amino acids (e.g., having a length of 30 amino acids (aa), 31 aa, 32 aa or 33 aa). In some cases, the TP33 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: HSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 142) and has a length of 33 amino acids. In some cases, the TP33 polypeptide comprises the amino acid sequence HSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 142) and has a length of 33 amino acids.

[0159] In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), where X1 is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and has a length of 33 amino acids to about 37 amino acids (e.g., 33 amino acids (aa), 34 aa, 35 aa, 36 aa, or 37 aa), or has a length of 30 amino acids to about 33 amino acids (e.g., 30 amino acids (aa), 31 aa, 32 aa, or 33 aa). In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), where X1 is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and the TP33 T cell epitope polypeptide has a length of 33 amino acids.

[0160] In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 144), where X1 is V, S, R or T, X2 is A or G, X3 is L or M, and X4 is I, L or V, and has a length of 33 amino acids to about 37 amino acids (e.g., has a length of 33 amino acids (aa), 34 aa, 35 aa, 36 aa, or 37 aa), or has a length of 30 amino acids to about 33 amino acids (e.g., has a length of 30 amino acids (aa), 31 aa, 32 aa, or 33 aa). In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 144), where X1 is V, S, R or T, X2 is A or G, X3 is L or M, and X4 is I, L or V, and the TP33 T cell epitope polypeptide has a length of 33 amino acids.

[0161] In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 145), where X1 is I, L, or V and X2 is V or I, and has a length of 33 amino acids to about 37 amino acids (e.g., a length of 33 amino acids (aa), 34 aa, 35 aa, 36 aa, or 37 aa), or a length of 30 amino acids to about 33 amino acids (e.g., a length of 30 amino acids (aa), 31 aa, 32 aa, or 33 aa). In some instances, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 145), where X1 is I, L or V and X2 is V or I, and the TP33 T cell epitope polypeptide has a length of 33 amino acids.

[0162] In some instances, the TP33 polypeptide comprises the amino acid sequence HSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIP (SEQ ID NO: 146) and has a length of 33 amino acids.

[0163] TP42-2 Polypeptide In some instances, the T42-2 polypeptide has a sequence similar to or similar to the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 147), at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about It comprises an amino acid sequence having about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity and has a length of 42 amino acids to about 46 amino acids (e.g., having a length of 42 amino acids (aa), 43 aa, 44 aa, 45 aa or 46 aa), or has a length of 38 amino acids to about 42 amino acids (e.g., having a length of 38 amino acids (aa), 39 aa, 40 aa, 41 aa or 42 aa). In some instances, the T42-2 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 147) and has a length of 42 amino acids. In some instances, the T42-2 polypeptide comprises the amino acid sequence KGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 147) and has a length of 42 amino acids.

[0164] In some instances, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), where Xi is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and has a length of 42 amino acids to about 46 amino acids (e.g., 42 amino acids (aa), 43 aa, 44 aa, 45 aa, or 46 aa), or has a length of 38 amino acids to about 42 amino acids (e.g., 38 amino acids (aa), 39 aa, 40 aa, 41 aa, or 42 aa). In some instances, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), where X1 is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and the T42-2 polypeptide has a length of 42 amino acids.

[0165] In some instances, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 149), where Xi is V, S, R or T, X2 is A or G, X3 is L or M, and X4 is I, L or V, and has a length of 42 amino acids to about 46 amino acids (e.g., has a length of 42 amino acids (aa), 43 aa, 44 aa, 45 aa or 46 aa), or has a length of 38 amino acids to about 42 amino acids (e.g., has a length of 38 amino acids (aa), 39 aa, 40 aa, 41 aa or 42 aa). In some instances, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 149), where X1 is V, S, R or T, X2 is A or G, X3 is L or M, and X4 is I, L or V, and the T42-2 polypeptide has a length of 42 amino acids.

[0166] In some instances, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 150), where X1 is I, L, or V and X2 is V or I, and has a length of 42 amino acids to about 46 amino acids (e.g., a length of 42 amino acids (aa), 43 aa, 44 aa, 45 aa, or 46 aa), or a length of 38 amino acids to about 42 amino acids (e.g., a length of 38 amino acids (aa), 39 aa, 40 aa, 41 aa, or 42 aa). In some instances, the T42-2 polypeptide comprises the following amino acid sequence: HSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 145), wherein X1 is I, L or V, X2 is V or I, and the T42-2 polypeptide has a length of 42 amino acids.

[0167] In some instances, the T42-2 polypeptide comprises the amino acid sequence KGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIP (SEQ ID NO: 151) and has a length of 42 amino acids.

[0168] TP65 Polypeptide In some instances, a TP65 T cell epitope polypeptide ("TP65 polypeptide") comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: TPIDTTIMAKNEVFCVDPX6KGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGX7SYGFQYS (SEQ ID NO: 152), wherein X6 is E, T, or V and X7 is S, A, or P, and has a length of 65 amino acids to 70 amino acids (e.g., 65, 66, 67, 68, 69, or 70 amino acids). In some instances, a TP65 T cell epitope polypeptide ("TP65 polypeptide") comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the following amino acid sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153), and has a length of 65 amino acids. In some instances, the TP has a length of 65 amino acids. In some instances, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153) and has a length of 65 amino acids.In some instances, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPTKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGASYGFQYS (SEQ ID NO: 154) and has a length of 65 amino acids. In some instances, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPVKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGPSYGFQYS (SEQ ID NO: 155).

[0169] TP240 Polypeptide In some instances, the TP240 polypeptide has the amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSSX1DATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGX2EGEIPFYGKAIPLX3X4IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTX5GDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 156), where X1 is T, V or Q and X2 is T, N, Q, X3 is H or S, X4 is E, S or A, X5 is V, T, Y, F or L, and X6 is S, Q or T), and has a length of 240 amino acids to 245 amino acids (e.g., 240, 241, 242, 243, 244 or 245 amino acids). In some cases, the TP has a length of 240 amino acids.

[0170] In some instances, the TP240 polypeptide has the following amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 157) and has a length of 240 amino acids. In some instances, the TP240 polypeptide has the following amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSVDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGNEGEIPFYGKAIPLSTIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTQGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 158) and has a length of 240 amino acids.

[0171] TP465 Polypeptide In some instances, the TP465 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to any one of the TP465 polypeptide amino acid sequences depicted in Figures 11A-11C, and has a length of 460 amino acids to 470 amino acids, for example, 465 amino acids in length.

[0172] In some instances, the TP465 polypeptide has the following amino acid sequence:

[0173] SFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIICDECHSTDATSILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLI FCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLEFWEGVFTG LTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRI (SEQ ID NO: 159), and has a length of about 465 amino acids.

[0174] TP156 Polypeptide In some instances, the TP156 polypeptide has the following amino acid sequence:

[0175] KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity, and has a length of about 150 amino acids to about 169 amino acids, for example, 156 amino acids.

[0176] TP29 Polypeptide In some cases, the TP29 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the TP29 amino acid sequence depicted in Figure 12, and has a length of about 29 amino acids. For example, in some cases, the TP29 polypeptide comprises the amino acid sequence: AIPLX(EA)X(VTYFL)IKGGRHLIFCHSKKKCDELAAKL (SEQ ID NO:61), wherein the first "X" is Glu or Ala and the second "X" is Val, Thr, Tyr, Phe, or Leu, and the TP29 polypeptide has a length of 29 amino acids.

[0177] TP50-NS2 Polypeptide In some cases, the TP50-NS2 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP50-NS2 amino acid sequence depicted in Figure 12 and has a length of about 50 amino acids. For example, in some cases, the TP50-NS2 polypeptide comprises the amino acid sequence: LGRWTGTYX(VI)YDHLTPLX(RS)DWAAAGLRDLAVAVEPVVFSPMEX(TK)KVITWGADT (SEQ ID NO: 62), wherein the first "X" is Val or Ile, the second "X" is Arg or Ser, and the third "X" is Thr or Lys, and the TP50-NS2 polypeptide has a length of 50 amino acids.

[0178] TP52 Polypeptides In some cases, the TP52 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP52 amino acid sequence depicted in Figure 12 and has a length of about 52 amino acids. For example, in some instances, a TP52 polypeptide comprises the amino acid sequence: AIPLX(EA)X(VTYFL)IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTX(SQ) (SEQ ID NO: 63), wherein the first "X" is Glu or Ala, the second "X" is Val, Thr, Tyr, Phe or Leu, and the third "X" is Ser or Gln, and the TP52 polypeptide has a length of 52 amino acids.

[0179] TP70 Polypeptide In some instances, the TP70 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to the TP70 amino acid sequence depicted in Figure 12, and has a length of about 70 amino acids. For example, in some instances, the TP70 polypeptide comprises the TP70 amino acid sequence depicted in Figure 12, wherein X is Ser or Gln, and the TP70 polypeptide has a length of 70 amino acids.

[0180] TP100 Polypeptide In some cases, the TP100 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP100 amino acid sequence depicted in Figure 12 and has a length of about 100 amino acids. For example, in some instances, the TP100 polypeptide comprises the TP100 amino acid sequence depicted in Figure 12, wherein the first "X" is Thr, Asn, Gln, His or Ser, the second "X" is Glue or Ala, the third "X" is Val, Thr, Tyr, Phe or Leu, and the fourth "X" is Ser or Gln, and the TP100 polypeptide has a length of 100 amino acids.

[0181] TP171 Polypeptide In some instances, TP171 comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP171 amino acid sequence depicted in FIG. 12 and has a length of about 171 amino acids.

[0182] TP228 Polypeptide In some instances, TP228 comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP228 amino acid sequence depicted in FIG. 12 and has a length of about 228 amino acids.

[0183] The TP228 polypeptide has the following TP228 amino acid sequence: LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSX1DATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGX2EGEIPFYGKAIPLX3X4IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTX5GDVVVVATDALMTGYTGDFDSVIDCN (SEQ ID NO: 161), where X1 is Thr or Val and X2 is Thr, As X2 is Glu or Ala, X3 is Val, Thr, Tyr, Phe or Leu, and X5 is Ser or Gln), and may have a length of 228 amino acids.

[0184] For example, a TP228 polypeptide has the following amino acid sequence: LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDC N (SEQ ID NO: 162), and may include an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or 100% amino acid sequence identity to N (SEQ ID NO: 162), and may include an amino acid sequence having 215 amino acids (aa) to 235 aa (e.g., 215 aa, 216 aa, 217 aa, 220 aa, 222 aa, 223 aa, 224 aa, 225 aa, 226 aa, 227 aa, 228 aa, 229 aa, 230 aa, 231 aa, 232 aa, 233 aa, 234 aa, 235 aa, 235 aa, 235 aa, 235 aa, 235 aa, 236 aa, 237 aa, 238 aa, 239 aa, 240 aa, 241 aa, 242 aa, 243 aa, 244 aa, 245 aa, 246 aa, 247 aa, 248 aa, 249 aa, 250 aa, 251 aa, 252 aa, 253 aa, 254 aa, 255 aa, 256 aa, 257 aa, 258 aa, 259 aa, 26 11, 218 aa, 219 aa, 220 aa, 221 aa, 222 aa, 223 aa, 224 aa, 225 aa, 226 aa, 227 aa, 228 aa, 229 aa, 230 aa, 231 aa, 232 aa, 233 aa, 234 aa or 235 aa).In some instances, the TP228 polypeptide has the following amino acid sequence: LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVV ATDALMTGFTGDFDSVIDCN (SEQ ID NO: 163), and has a length of 228 amino acids.

[0185] TP553 Polypeptide In some cases, the TP553 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP553 amino acid sequence depicted in Figure 12 and has a length of about 553 amino acids.

[0186] TP778 Polypeptide In some cases, the TP778 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP778 amino acid sequence depicted in FIG. 12 and has a length of about 778 amino acids.

[0187] TP1987 Polypeptide In some cases, the TP1987 polypeptide comprises an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the TP1987 amino acid sequence depicted in Figure 12 and has a length of about 1987 amino acids.

[0188] Compositions containing a single TP In some instances, the immunogenic compositions of the disclosure comprise a) a single TP, including: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP46 TP1987 polypeptide, and b) a TP selected from the group consisting of: a TP29 polypeptide, a TP50-NS2 polypeptide, a TP52 polypeptide, a TP70 polypeptide, a TP100 polypeptide, a TP171 polypeptide, a TP228 polypeptide, a TP553 polypeptide, a TP778 polypeptide, and a TP1987 polypeptide; and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure comprises a) a single TP selected from the group consisting of: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide, and xxiv) a TP1987 polypeptide; and b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition containing saponin.

[0189] In some cases, the immunogenic composition of the present disclosure comprises a) a single TP selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) a single TP selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0190] In some cases, the immunogenic composition of the present disclosure comprises a) a single TP selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) a single TP selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0191] In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP35-NS3 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP35-NS3 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0192] In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP27 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0193] In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP48 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP48 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0194] In some cases, the immunogenic composition of the present disclosure comprises a) a single TP, the TP being a TP50C polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) a single TP, the TP being a TP50C polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0195] In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP65 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin. In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0196] In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP240 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin. In some cases, the immunogenic composition of the disclosure includes a) a single TP, the TP being a TP240 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0197] In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP156 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP156 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0198] In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP465 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure comprises a) a single TP, the TP being a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0199] Composition containing two TPs In some cases, the immunogenic compositions of the disclosure comprise a) only two TPs: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, a TP29 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide and xxiv) a TP1987 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure comprises: a) only two TPs selected from the group consisting of: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide, and xxiv) a TP1987 polypeptide; and b) an HCV E1 polypeptide, an HCV E2 polypeptide or HCV E1 / E2 heterodimer and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin.

[0200] In some cases, the immunogenic composition of the present disclosure comprises a) only two TPs, the two TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) only two TPs, the two TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0201] In some cases, the immunogenic composition of the present disclosure comprises a) only two TPs, the two TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) only two TPs, the two TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0202] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP27 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0203] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP27 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0204] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP27 polypeptide and a TP50C polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP27 polypeptide and a TP50C polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0205] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP48 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP48 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0206] In some cases, the immunogenic composition of the present disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP50C polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the present disclosure includes a) two TPs, the two TPs being a TP35-NS3 polypeptide and a TP50C polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0207] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP50C polypeptide, and b) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP50C polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0208] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP156 polypeptide and a TP465 polypeptide, and b) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP156 polypeptide and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0209] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP156 polypeptide and a TP48 polypeptide, and b) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP156 polypeptide and a TP48 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0210] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP465 polypeptide, and b) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0211] In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP65 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure includes a) two TPs, the two TPs being a TP48 polypeptide and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0212] In some cases, the immunogenic composition of the present disclosure includes a) two TPs, the two TPs being a TP465 polypeptide and a TP65 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the present disclosure includes a) two TPs, the two TPs being a TP465 polypeptide and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0213] Composition containing 3 TPs In some cases, the immunogenic compositions of the disclosure comprise a) only three TPs: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, a TP29 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide and xxiv) a TP1987 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure comprises a) only three TPs selected from the group consisting of: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide, and xxiv) a TP1987 polypeptide; and b) an HCV E1 polypeptide, an HCV E2 polypeptide or HCV E1 / E2 heterodimer and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin.

[0214] In some cases, the immunogenic composition of the present disclosure comprises a) only three TPs, the three TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) only three TPs, the three TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0215] In some cases, the immunogenic composition of the present disclosure includes a) only three TPs, selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) only three TPs, selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0216] In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP35-NS3 polypeptide, a TP48 polypeptide, and a TP27 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP35-NS3 polypeptide, a TP48 polypeptide, and a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0217] In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP50C polypeptide, a TP48 polypeptide, and a TP27 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP50C polypeptide, a TP48 polypeptide, and a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0218] In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP50C polypeptide, a TP48 polypeptide, and a TP35-NS3 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP50C polypeptide, a TP48 polypeptide, and a TP35-NS3 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0219] In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP50C polypeptide, a TP27 polypeptide, and a TP35-NS3 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) three TPs, the three TPs being a TP50C polypeptide, a TP27 polypeptide, and a TP35-NS3 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0220] In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP465 polypeptide, and a TP48 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP465 polypeptide, and a TP48 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0221] In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP465 polypeptide, and a TP65 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP465 polypeptide, and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0222] In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP465 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP465 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0223] In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) three TPs, the three TPs being a TP156 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0224] Composition containing 4 TPs In some cases, the immunogenic compositions of the disclosure comprise a) only four TPs: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide and xxiv) a TP1987 polypeptide, and b) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.In some cases, the immunogenic composition of the disclosure comprises: a) only four TPs selected from the group consisting of: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP23 polypeptide, iv) a TP27 polypeptide, v) a TP35-NS4 polypeptide, vi) a TP42 polypeptide, vii) a TP45 polypeptide, viii) a TP48 polypeptide, ix) a TP33 polypeptide, x) a TP42-2 polypeptide, xi) a TP65 polypeptide, xii) a TP240 polypeptide, xiii) a TP156 polypeptide, xiv) a TP465 polypeptide, xv) a TP29 polypeptide, xvi) a TP50-NS2 polypeptide, xvii) a TP52 polypeptide, xviii) a TP70 polypeptide, xix) a TP100 polypeptide, xx) a TP171 polypeptide, xxi) a TP228 polypeptide, xxii) a TP553 polypeptide, xxiii) a TP778 polypeptide, and xxiv) a TP1987 polypeptide; and b) an HCV E1 polypeptide, an HCV E2 polypeptide or HCV E1 / E2 heterodimer and c) SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising saponin.

[0225] In some cases, the immunogenic composition of the present disclosure comprises a) only four TPs, the four TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure comprises a) only four TPs, the four TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP240 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0226] In some cases, the immunogenic composition of the present disclosure includes a) only four TPs, the four TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) only four TPs, the four TPs being selected from the group consisting of a TP35-NS3 polypeptide, a TP50C polypeptide, a TP27 polypeptide, a TP48 polypeptide, a TP65 polypeptide, a TP240 polypeptide, a TP156 polypeptide, and a TP465 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0227] In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP35-NS3 polypeptide, a TP48 polypeptide, a TP50C polypeptide, and a TP27 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP35-NS3 polypeptide, a TP48 polypeptide, a TP50C polypeptide, and a TP27 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0228] In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP240 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP50C polypeptide, and b) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP240 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP50C polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated into a liposomal composition comprising i) a stable emulsion or ii) a saponin.

[0229] In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP156 polypeptide, a TP465 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, and b) an SLA formulated in a liposomal composition comprising i) a stable emulsion or ii) a saponin.In some cases, the immunogenic composition of the present disclosure includes a) four TPs, the four TPs being a TP156 polypeptide, a TP465 polypeptide, a TP48 polypeptide, and a TP65 polypeptide, b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer, and c) an SLA formulated in i) a stable emulsion or ii) a liposomal composition comprising a saponin.

[0230] Compositions Comprising T-Cell Epitope Fusion Polypeptides As described above, in some cases, the immunogenic compositions of the present disclosure include a T cell epitope fusion polypeptide, i.e., a fusion polypeptide that includes two or more of the above T cell epitope polypeptides. T cell epitope fusion polypeptides are also referred to herein as "TP fusion polypeptides."

[0231] In some cases, the TP fusion polypeptide does not include a linker peptide between any two TP polypeptides. In some cases, the TP fusion polypeptide includes a linker peptide between any two TP polypeptides. When the TP fusion polypeptide includes one or more linker peptides, the one or more linker peptides are independently 1 to 10 amino acids in length (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids in length). When the TP fusion polypeptide comprises one or more linker peptides, the one or more linker peptides are independently selected from, for example, (GGGGS)n (SEQ ID NO: 163), where n is an integer from 1 to 5 (e.g., n is 1, 2, 3, 4 or 5); AAAGG (SEQ ID NO: 164); (EAAAK)n (SEQ ID NO: 165); A(EAAAK)nA (SEQ ID NO: 166); A(EAAAK)nALEA(EAAAK)nA (SEQ ID NO: 167); (Lys-Pro)n (SEQ ID NO: 168), (Glu-Pro)n (SEQ ID NO: 169), (Thr-Pro-Arg)n (SEQ ID NO: 170) or (Ala-Pro)n (SEQ ID NO: 171), where n is an integer from 1 to 5 (e.g., n is 1, 2, 3, 4 or 5).

[0232] In some cases, the TP fusion polypeptide comprises only two TP polypeptides. For example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide and a TP35-NS3 polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide and a TP48 polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide and a TP50C polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP35-NS3 polypeptide and a TP48 polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP35-NS3 polypeptide and a TP50C polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP50C polypeptide and a TP48 polypeptide. In some cases, the TP fusion polypeptide comprises only two TP polypeptides and does not comprise any other polypeptides.

[0233] In some cases, the TP fusion polypeptide comprises only three TP polypeptides. For example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide, a TP35-NS3 polypeptide, and a TP48 polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide, a TP48 polypeptide, and a TP50C polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP35-NS3 polypeptide, a TP48 polypeptide, and a TP50C polypeptide. As another example, in some cases, the TP fusion polypeptide comprises a TP27 polypeptide, a TP35-NS3 polypeptide, and a TP50C polypeptide. In some cases, the TP fusion polypeptide comprises only three TP polypeptides, and does not comprise any other polypeptides.

[0234] In some cases, the TP fusion polypeptide comprises four TP polypeptides (e.g., TP27, TP35-NS3, TP50C and TP48). In some cases, the TP fusion polypeptide comprises all four of the above TP polypeptides and does not comprise any other polypeptide. In some cases, the TP fusion polypeptide has a total length of 160 amino acids to 190 amino acids (e.g., 160 amino acids to 165 amino acids, 165 amino acids to 170 amino acids, 170 amino acids to 175 amino acids, 175 amino acids to 180 amino acids, 180 amino acids to 185 amino acids, or 185 amino acids to 190 amino acids). In some cases, the TP fusion polypeptide has a total length of 160 amino acids.

[0235] The four TP polypeptides (e.g., TP27, TP35-NS3, TP50C and TP48) can be arranged in any order in the TP fusion polypeptide. 1) For example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) TP35-NS3 polypeptide, ii) TP27 polypeptide, iii) TP48 polypeptide and iv) TP50C polypeptide. 2) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) TP35-NS3 polypeptide, ii) TP27 polypeptide, iii) TP50C polypeptide and iv) TP48 polypeptide. 3) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) TP35-NS3 polypeptide, ii) TP48 polypeptide, iii) TP27 polypeptide and iv) TP50C polypeptide. 4) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP35-NS3 polypeptide, ii) a TP48 polypeptide, iii) a TP50C polypeptide, and iv) a TP27 polypeptide. 5) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP27 polypeptide, and iv) a TP48 polypeptide. 6) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP35-NS3 polypeptide, ii) a TP50C polypeptide, iii) a TP48 polypeptide, and iv) a TP27 polypeptide. 7) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP27 polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP50C polypeptide, and iv) a TP48 polypeptide. 8) As another example, in some cases, a TP fusion polypeptide comprises, from N-terminus to C-terminus, in this order: i) a TP27 polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP48 polypeptide, and iv) a TP50C polypeptide.9) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP27 polypeptide, ii) a TP48 polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP50C polypeptide. 10) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP27 polypeptide, ii) a TP48 polypeptide, iii) a TP50C polypeptide, and iv) a TP35-NS3 polypeptide. 11) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP27 polypeptide, ii) a TP50C polypeptide, iii) a TP48 polypeptide, and iv) a TP35-NS3 polypeptide. 12) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP27 polypeptide, ii) a TP50C polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP48 polypeptide. 13) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP48 polypeptide, ii) a TP27 polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP50C polypeptide. 14) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP48 polypeptide, ii) a TP27 polypeptide, iii) a TP50C polypeptide, and iv) a TP35-NS3 polypeptide. 15) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP48 polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP27 polypeptide, and iv) a TP50C polypeptide. 16) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP48 polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP50C polypeptide, and iv) a TP27 polypeptide. 17) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in this order: i) a TP48 polypeptide, ii) a TP50C polypeptide, iii) a TP27 polypeptide, and iv) a TP35-NS3 polypeptide.18) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP48 polypeptide, ii) a TP50C polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP27 polypeptide. 19) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP27 polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP48 polypeptide. 20) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP27 polypeptide, iii) a TP48 polypeptide, and iv) a TP35-NS3 polypeptide. 21) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP27 polypeptide, and iv) a TP48 polypeptide. 22) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP35-NS3 polypeptide, iii) a TP48 polypeptide, and iv) a TP27 polypeptide. 23) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP48 polypeptide, iii) a TP27 polypeptide, and iv) a TP35-NS3 polypeptide. 24) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP50C polypeptide, ii) a TP48 polypeptide, iii) a TP35-NS3 polypeptide, and iv) a TP27 polypeptide.

[0236] As one non-limiting example, a TP fusion polypeptide comprises, in order from N-terminus to C-terminus: i) a TP35-NS3 polypeptide, ii) a TP27 polypeptide, iii) a TP48 polypeptide, and iv) a TP50C polypeptide. In some cases, the TP fusion polypeptide has at least 80% (at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) amino acid sequence identity to the amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKLEQIKGGRHLIFCHSKKKCDELAAKLRILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 172). and wherein i) KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO:79) is a TP35-NS3 polypeptide; ii) LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO:103) is a TP27 polypeptide; iii) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO:136) is a TP48 polypeptide; and iv) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO:87) is a TP50C polypeptide. In some cases, the TP fusion polypeptide has a total length of 160 amino acids to 190 amino acids (e.g., 160 amino acids to 165 amino acids, 165 amino acids to 170 amino acids, 170 amino acids to 175 amino acids, 175 amino acids to 180 amino acids, 180 amino acids to 185 amino acids, or 185 amino acids to 190 amino acids). In some cases, the TP fusion polypeptide has a total length of 160 amino acids.

[0237] In some cases, the TP fusion polypeptide comprises a TP240 polypeptide, a TP48 polypeptide, a TP65 polypeptide and a TP50C polypeptide, and does not comprise any other polypeptide. The total length of the TP fusion polypeptide may be 410 amino acids to 415 amino acids (e.g., 410, 411, 412, 413, 414 or 415 amino acids). In some cases, the TP fusion polypeptide has a length of 410 amino acids. The four TP polypeptides may be arranged in any order in the TP fusion polypeptide. For example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus, in the order: i) a TP240 polypeptide, ii) a TP48 polypeptide and iii) a TP65 polypeptide, iv) a TP50C polypeptide. As an example, a TP fusion polypeptide may comprise an amino acid sequence having at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence depicted in FIG. 10 (wherein X1 is T, V or Q, X2 is T, N, Q, H or S, X3 is E, S or A, X4 is V, T, Y, F or L, X5 is S, Q or T, X6 is E, T or V, and X7 is S, A or P), and the TP fusion polypeptide has a length of 410 amino acids to 415 amino acids (e.g., 410, 411, 412, 413, 414 or 415 amino acids).

[0238] HCV E1 Polypeptides, HCV E2 Polypeptides, and HCV E1 / E2 Heterodimers As noted above, in some cases, the immunogenic compositions of the disclosure include an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0239] E1 Polypeptide HCV E1 polypeptides suitable for inclusion in the immunogenic compositions of the disclosure, or for inclusion in HCV E1 / E2 heterodimers present in the immunogenic compositions of the disclosure, may have a length of about 100 amino acids (aa) to about 150 aa, about 150 aa to about 175 aa, about 175 aa to about 195 aa, about 131 aa to about 175 aa, or about 175 aa to about 193 aa. In some cases, the HCV E1 polypeptide is an HCV E1 ectodomain polypeptide. In some cases, the HCV E1 polypeptide is a full-length HCV E1 polypeptide.

[0240] In Figures 1A-1C, the amino acid sequence of E1 is from amino acid 192 to amino acid 383. In Figures 2A-2C, the amino acid sequence of E1 is from amino acid 192 to amino acid 383. In Figures 3A-3C, the amino acid sequence of E1 is from amino acid 192 to amino acid 384. In Figures 4A-4B, the amino acid sequence of E1 is from amino acid 192 to amino acid 383. Amino acids from about 170 to about 191 serve as a signal sequence for E1. As used herein, "E1 polypeptide" includes precursor E1 proteins that include a signal sequence, includes mature E1 polypeptides that lack this sequence, and includes E1 polypeptides that have a heterologous signal sequence. E1 polypeptides may include a C-terminal membrane anchor sequence, which occurs at about amino acid position 360-383 (see, e.g., WO96 / 04301). In some cases, suitable E1 polypeptides lack a C-terminal portion that includes a transmembrane region. For example, in some cases, a suitable E1 polypeptide lacks the C-terminus from amino acid 330 to amino acid 384, or from amino acid 360 to amino acid 384. The E1 polypeptide can be an E1 polypeptide of any genotype, subtype or isolate of HCV. Included in the E1 / E2 heterodimers of the present disclosure are E1 polypeptides of genotype 1 and E1 polypeptides of genotype 3.

[0241] The E1 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E1 polypeptide depicted in Figures 1A-1C, 2A-2C, 3A-3C or 4A-4B.

[0242] The E1 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E1 polypeptide depicted in Figures 1A-1C. For example, an E1 polypeptide of genotype 1A may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence identified as 1A and depicted in Figures 1A-1C. For example, an E1 polypeptide of genotype 1B may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence identified as 1B and depicted in Figures 1A-1C.For example, an E1 polypeptide of genotype 1C may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence identified as 1C and depicted in Figures 1A-1C.

[0243] The E1 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E1 polypeptide depicted in Figures 2A-2C. For example, an E1 polypeptide of genotype 2A may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence identified as 2A and depicted in Figures 2A-2C. For example, an E1 polypeptide of genotype 2B may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence identified as 2B and depicted in Figures 2A-2C.

[0244] The E1 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the consensus E1 polypeptide amino acid sequence depicted in Figures 3A-3C.

[0245] The E1 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E1 polypeptide depicted in Figures 4A-4B. For example, an E1 polypeptide of genotype 7A may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 192-383 of the amino acid sequence depicted in Figures 4A-4B.

[0246] E2 Polypeptide An E2 polypeptide suitable for inclusion in an immunogenic composition of the disclosure, or for inclusion in an HCV E1 / E2 heterodimer present in an immunogenic composition of the disclosure, may have a length of about 200 amino acids (aa) to about 250 aa, about 250 aa to about 275 aa, about 275 aa to about 300 aa, about 300 aa to about 325 aa, about 325 aa to about 350 aa, or about 350 aa to about 365 aa. In some cases, the HCV E2 polypeptide is an HCV E2 ectodomain polypeptide. In some cases, the HCV E2 polypeptide is a full-length HCV E2 polypeptide.

[0247] In Figures 1A-AC, the amino acid sequence of E2 is from amino acid 384 to amino acid 746. In Figures 2A-2B, the amino acid sequence of E2 is from amino acid 384 to amino acid 751. In Figures 3A-3C, the amino acid sequence of E2 is from amino acid 385 to amino acid 754. In Figures 4A-4B, the amino acid sequence of E2 is from amino acid 384 to amino acid 750. As used herein, "E2 polypeptide" includes precursor E2 proteins that include a signal sequence, including mature E2 polypeptides that lack this sequence, and E2 polypeptides that have a heterologous signal sequence. An E2 polypeptide may include a C-terminal membrane anchor sequence, which occurs at approximately amino acid position 715-730 and may extend to approximately amino acid residue 746 (see Lin et al., J. Virol. (1994) 68:5063-5073).

[0248] In some instances, the E2 polypeptide lacks a portion of its C-terminal region, e.g., from about amino acid 715 to the C-terminus, from about amino acid 625 to the C-terminus, from about amino acid 661 to the C-terminus, from about amino acid 655 to the C-terminus, from about amino acid 500 to the C-terminus, where the amino acid numbering is in accordance with the numbering in Figures 1A-1C. See, e.g., U.S. Patent No. 6,521,423.

[0249] An E2 polypeptide suitable for inclusion in an immunogenic composition of the present disclosure may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 1A-1C, 2A-2C, 3A-3C or 4A-4B. An E2 polypeptide suitable for inclusion in an immunogenic composition of the present disclosure may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70% or at least about 75% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 1A-1C, 2A-2C, 3A-3C or 4A-4B.

[0250] The E2 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 1A-1C. For example, an E2 polypeptide of genotype 1 can comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-746 of the amino acid sequence depicted in Figures 1A-1C. For example, an E2 polypeptide of genotype 1A may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-746 of the amino acid sequence identified as 1A and depicted in Figures 1A-1C.For example, an E2 polypeptide of genotype 1B may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-746 of the amino acid sequence identified as 1B and depicted in Figures 1A-1C. For example, an E2 polypeptide of genotype 1C may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-746 of the amino acid sequence identified as 1C and depicted in Figures 1A-1C.

[0251] The E2 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 2A-2C. For example, an E2 polypeptide can comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-751 of the amino acid sequence depicted in Figures 2A-2C. For example, an E2 polypeptide of genotype 2A can comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-751 of the "consensus" amino acid sequence depicted in Figures 2A-2C. For example, an E2 polypeptide of genotype 2B may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-751 of the "consensus" amino acid sequence depicted in Figures 2A-2C.

[0252] The E2 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 3A-3C. For example, an E2 polypeptide of genotype 3 can comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 385-754 of the amino acid sequence depicted in Figures 3A-3C. For example, an E2 polypeptide of genotype 3A may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 385-754 of the amino acid sequence identified as 3A and depicted in Figures 3A-3C.For example, an E2 polypeptide of genotype 3B may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 385-754 of the amino acid sequence identified as 3B and depicted in Figures 3A-3C. For example, an E2 polypeptide of genotype 3K may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 385-754 of the amino acid sequence identified as 3K and depicted in Figures 3A-3C.

[0253] The E2 polypeptide may comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to the amino acid sequence of the E2 polypeptide depicted in Figures 4A-4B. For example, an E2 polypeptide of genotype 7A can comprise an amino acid sequence having at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity to amino acids 384-750 of the amino acid sequence depicted in Figures 4A-4B.

[0254] HCV E1 / E2 heterodimer HCV E1 / E2 heterodimers suitable for use in the immunogenic compositions of the present disclosure include HCV E1 / E2 heterodimers comprising a wild-type HCV E1 polypeptide, HCV E1 / E2 heterodimers comprising a wild-type HCV E2 polypeptide, HCV E1 / E2 heterodimers comprising a variant HCV E1 polypeptide, and HCV E1 / E2 heterodimers comprising a variant HCV E2 polypeptide. HCV E2 polypeptides suitable for use in the immunogenic compositions of the present disclosure include wild-type E2 polypeptides and variant E2 polypeptides. HCV E1 polypeptides suitable for use in the immunogenic compositions of the present disclosure include wild-type E1 polypeptides and variant E1 polypeptides. HCV E1 / E2 heterodimers may include any of the HCV E1 polypeptides discussed above and any of the HCV E2 polypeptides discussed above.

[0255] container The present disclosure provides a container comprising an immunogenic composition of the present disclosure. The container can be, for example, a syringe, an ampoule, etc. In some cases, the container is sterile. In some cases, both the container and the immunogenic composition are sterile.

[0256] Methods for inducing an immune response The present disclosure provides a method for inducing an immune response (e.g., a protective immune response) against at least one HCV genotype in a mammalian subject, the method comprising administering to the individual an effective one of the immunogenic compositions of the present disclosure.

[0257] In some cases, a prime-boost vaccine protocol is used. In some cases, a first (priming) immunogenic composition is administered, and after a period of time, a second (booster) immunogenic composition is administered. In some cases, the first and second immunogenic compositions are the same. In some cases, the first and second immunogenic compositions are different. For example, in some cases, the first immunogenic composition comprises a first TP fusion polypeptide, and the second immunogenic composition comprises a second TP fusion polypeptide having an amino acid sequence different from the first TP fusion polypeptide. The second immunogenic composition may be administered 1 day to 1 year after administration of the first immunogenic composition. For example, the second immunogenic composition may be administered 1 day to 1 week, 1 week to 2 weeks, 2 weeks to 1 month, 1 month to 2 months, 2 months to 6 months, or 6 months to 1 year after administration of the first immunogenic composition.

[0258] General Considerations The immunogenic compositions of the present disclosure are generally administered to human subjects who: i) have HCV infection, or ii) are at risk of acquiring HCV infection (e.g., are at a greater risk than the general population of acquiring HCV infection), or iii) are naïve with respect to HCV infection, to prevent or at least partially halt the onset of the disease and its complications. An amount adequate to accomplish this is defined as a "therapeutically effective dose" or "therapeutically effective amount." "Prophylactic" use of a subject immunogenic composition generally refers to administration to individuals who have not been infected with HCV (e.g., "naïve" individuals). "Therapeutic" use of a subject immunogenic composition may refer to "prophylactic" use (administration to individuals who have not been infected with HCV) and / or administration to individuals with HCV infection. A "therapeutically effective amount" of an immunogenic composition of the present disclosure may be an amount that, when administered in one or more doses to an individual not infected with HCV, is effective to induce an immune response in the individual against HCV. A "therapeutically effective amount" of an immunogenic composition of the disclosure can be an amount that, when administered in one or more doses to an individual infected with HCV, is effective to enhance an immune response in the individual against HCV.

[0259] Amounts effective for therapeutic use will vary depending, for example, on the method of administration, the weight and general health of the patient, and the judgment of the prescribing physician. Single or multiple doses of a subject immunogenic composition may be administered, depending on the dosage and frequency required and tolerated by the patient, and the route of administration.

[0260] In some cases, an effective amount of an immunogenic composition of the present disclosure is an amount that, when administered to an individual in one or more doses, is effective to induce an antibody response (e.g., a neutralizing antibody response) against HCV in the individual. For example, antibodies against HCV (e.g., extracellular HCV) and / or against HCV-infected cells may be induced.

[0261] An effective amount of an immunogenic composition of the disclosure can be an amount that, when administered to an individual in one or more doses, is effective to induce a neutralizing antibody response against HCV of various genotypes (e.g., genotype 1, genotype 3, etc.). A neutralizing antibody response reduces binding of HCV to one or more HCV host receptors and inhibits HCV entry into cells.

[0262] In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the disclosure, when administered to an individual in one or more doses, will elicit a cytotoxic T lymphocyte (CTL) response (e.g., CD8 + The amount is effective to induce a CTL response against HCV-infected cells.

[0263] In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the disclosure refers to an amount that, when administered to an individual in one or more doses, increases the number of helper T lymphocytes (e.g., CD4 + The amount is effective to induce the expression of a cellular T cell.

[0264] In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the present disclosure is an amount that, when administered to an individual in one or more doses, is effective to induce an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response against HCV genotype 1. In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the present disclosure is an amount that, when administered to an individual in one or more doses, is effective to induce an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response against HCV genotype 3. In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the present disclosure is an amount that, when administered to an individual in one or more doses, is effective to induce an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response against HCV genotype 1 and HCV genotype 3. In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the present disclosure is an amount that, when administered to an individual in one or more doses, is effective to induce an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response against any genotype of HCV. ... + In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the present disclosure is an amount that is effective to induce a CD4 T cell response against HCV genotypes 1-6 when administered to an individual in one or more doses. + This is an amount that is effective to induce a T cell response.

[0265] The immunogenic compositions of the present disclosure are generally administered in an amount effective to induce an immune response, e.g., a humoral immune response (e.g., an antibody response) and / or a CTL response, in a mammalian subject. The effective amount of E1 / E2, E1 or E2 polypeptide for immunization varies and may generally range from about 1 μg to 100 μg per 70 kg patient, e.g., about 5 μg / 70 kg to about 50 μg / 70 kg. Substantially higher doses of HCV E1 / E2, E1 or E2 polypeptide (e.g., 10 mg to 100 mg or more) may be appropriate for oral, nasal or topical administration routes. In some cases, the dose of the immunogenic composition of the present disclosure includes an amount of HCV E1 / E2 heterodimer between 4 μg and 100 μg. For example, in some cases, a dose of the immunogenic composition of the present disclosure comprises an amount of HCV E1 / E2 heterodimer between 4 μg and 5 μg, 5 μg and 10 μg, 10 μg and 15 μg, 15 μg and 20 μg, 20 μg and 25 μg, 25 μg and 30 μg, 30 μg and 40 μg, 40 μg and 50 μg, 50 μg and 60 μg, 60 μg and 70 μg, 70 μg and 80 μg, 80 μg and 90 μg, or 90 μg and 100 μg. In some cases, a dose of the immunogenic composition of the present disclosure comprises an amount of HCV E1 / E2 heterodimer between about 100 μg and about 200 μg.

[0266] In some cases, the amount of T cell epitope polypeptide in a given dose ranges from 0.1 μg to 125 μg, for example, suitable doses of T cell epitope polypeptide range from 0.1 μg to 0.5 μg, 0.5 μg to 1 μg, 1 μg to 5 μg, 5 μg to 10 μg, 10 μg to 15 μg, 15 μg to 20 μg, 20 μg to 25 μg, 25 μg to 30 μg, 30 μg to 40 μg, 40 μg to 50 μg, 50 μg to 60 μg, 60 μg to 75 μg, 75 μg to 100 μg, or 100 μg to 125 μg. In some cases, when two or more different T cell epitope polypeptides are included in the immunogenic composition, the dose will include 0.5 μg to 125 μg of each T cell epitope polypeptide. In some cases, when two (or more) different T cell epitope polypeptides are included in the immunogenic composition, the dose may include 1 μg to 10 μg (e.g., 1 μg, 2 μg, 3 μg, 4 μg, 5 μg, 6 μg, 7 μg, 8 μg, 9 μg, or 10 μg) of each T cell epitope polypeptide. As one non-limiting example, when an immunogenic composition of the present disclosure includes two or more different T cell epitope polypeptides, the composition may include 1 μg of each different T cell epitope polypeptide. As another non-limiting example, when an immunogenic composition of the present disclosure includes two or more different T cell epitope polypeptides, the composition may include 3 μg of each different T cell epitope polypeptide. As another non-limiting example, when an immunogenic composition of the present disclosure includes two or more different T cell epitope polypeptides, the composition may include 6 μg of each different T cell epitope polypeptide.

[0267] In some cases, a single dose of the immunogenic composition of the disclosure comprises: a) HCV E1 / E2 heterodimer in an amount of about 10 μg to about 15 μg (e.g., 10 μg, 11 μg, 12 μg, 13 μg, 14 μg, or 15 μg of E1 / E2 heterodimer); and b) two or more different T cell epitope polypeptides in an amount of about 5 μg of each different T cell epitope polypeptide to about 15 μg of each different T cell epitope polypeptide (e.g., 5 μg, 6 μg, 7 μg, 8 μg, 9 μg, 10 μg, 11 μg, 12 μg, 13 μg, 14 μg, or 15 μg of each different T cell epitope polypeptide). As one non-limiting example, in some cases, a single dose of an immunogenic composition of the disclosure comprises a) 15 μg of E1 / E2 heterodimer and b) 40 μg of T cell epitope polypeptides (10 μg each of TP35-NS3, TP50C, TP27 and TP48).

[0268] In some cases, a dose of an immunogenic composition of the disclosure comprises an E1 / E2 heterodimer and a T cell epitope polypeptide, and the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is about 0.1:1 to about 25:1. For example, the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in an immunogenic composition of the disclosure is about 0.1:1 to about 0.2:1, about 0.2:1 to 0.3:1, about 0.3:1 to about 0.4:1, about 0.4:1 to about 0.5:1, or about 0.5:1 to 1:1. When multiple different T cell epitope polypeptides are present in the immunogenic composition of the present disclosure, the molar ratio of the different T cell epitope polypeptides to the E1 / E2 heterodimer can each independently be about 0.1:1 to about 0.2:1, about 0.1:1 to about 0.5:1, about 0.2:1 to about 0.3:1, about 0.3:1 to about 0.4:1, about 0.4:1 to about 0.5:1, or about 0.5:1 to 1:1. As another example, the molar ratio of any given T cell epitope polypeptide to the E1 / E2 heterodimer is 1:1 to 25:1, e.g., 1:1 to 5:1, 5:1 to 10:1, 10:1 to 15:1, 15:1 to 20:1, or 20:1 to 25:1. In some cases, the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the immunogenic composition of the present disclosure is about 10:1 to 20:1. In some cases, the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the immunogenic composition of the present disclosure is about 10:1 to 15:1. In some cases, the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the composition of the present disclosure is 15:1.

[0269] As a non-limiting example, in some cases, an immunogenic composition of the disclosure comprises an E1 / E2 heterodimer and four different T cell epitope polypeptides, wherein the molar ratio of each of the T cell epitope polypeptides to the E1 / E2 heterodimers in the composition is independently from about 0.1:1 to about 25:1. As an example, in some cases, the immunogenic compositions of the disclosure include a) an E1 / E2 heterodimer and b) a TP50C polypeptide ("TP50C"), a TP35-NS3 polypeptide ("TP35-NS3"), a TP27 polypeptide ("TP27") and a TP48 polypeptide ("TP48"), wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 0.1:1 to 0.5:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 0.1:1 to 0.5:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 0.1:1 to 0.5:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 0.1:1 to 0.5:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 0.5:1 to 1:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 0.5:1 to 1:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 0.5:1 to 1:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 0.5:1 to 1:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 1:1 to 5:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 1:1 to 5:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 1:1 to 5:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 1:1 to 5:1.As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 5:1 to 10:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 5:1 to 10:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 5:1 to 10:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 5:1 to 10:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 10:1 to 25:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 10:1 to 25:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 10:1 to 25:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 10:1 to 25:1. As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 0.1:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 0.1:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 0.1:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 0.1:1. As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 0.3:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 0.3:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 0.3:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 0.3:1.As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 0.5:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 0.5:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 0.5:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 0.5:1. As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 1:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 1:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 1:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 1:1. As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 3:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 3:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 3:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 3:1. As another example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP50C to E1 / E2 heterodimer is 9:1, ii) the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 9:1, iii) the molar ratio of TP27 to E1 / E2 heterodimer is 9:1, and iv) the molar ratio of TP48 to E1 / E2 heterodimer is 9:1.As another example, in some cases, the immunogenic composition of the present disclosure comprises i) an E1 / E2 heterodimer and ii) four different T cell epitope polypeptides, the four different T cell epitope polypeptides being a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide. As an example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP50C polypeptide, a TP35-NS3 polypeptide, a TP27 polypeptide, and a TP48 polypeptide, the molar ratio of i) TP50C to E1 / E2 heterodimer is 3:1, the molar ratio of TP35-NS3 to E1 / E2 heterodimer is 3:1, the molar ratio of TP27 to E1 / E2 heterodimer is 3:1, and the molar ratio of TP48 to E1 / E2 heterodimer is 9:1. The amino acid sequences of the TP50C, TP35-NS3, TP27 and TP48 polypeptides are provided above. In some cases, the TP50C polypeptide comprises the following amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87) and has a length of 50 amino acids, the TP35-NS3 polypeptide comprises the following amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79) and has a length of 35 amino acids, the TP27 polypeptide comprises the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103) and has a length of 27 amino acids, and the TP48 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136) and has a length of 48 amino acids.

[0270] As a non-limiting example, in some cases, an immunogenic composition of the disclosure comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is, each independently, about 0.1:1 to about 25:1. As an example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide ("TP465") and a TP48 polypeptide ("TP48"), wherein i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1, and ii) the molar ratio of TP48 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.5:1 to 1:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1 to 5:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 5:1 to 10:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 10:1 to 25:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 10:1 to 25:1.As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 1:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 3:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 9:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 9:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.1:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 0.1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.3:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 0.3:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.5:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 0.5:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, wherein i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 9:1.As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP48 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 9: 1 and ii) the molar ratio of TP48 to E1 / E2 heterodimer is 3: 1. The amino acid sequences of the TP465 polypeptide and the TP48 polypeptide are provided above.

[0271] As a non-limiting example, in some cases, the immunogenic composition of the disclosure comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is, each independently, about 0.1:1 to about 25:1. As an example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide ("TP465") and a TP65 polypeptide ("TP65"), wherein i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1, and ii) the molar ratio of TP65 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) E1 / E2 heterodimer and b) TP465 polypeptide and TP65 polypeptide, i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.5:1 to 1:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) E1 / E2 heterodimer and b) TP465 polypeptide and TP65 polypeptide, i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1 to 5:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) E1 / E2 heterodimer and b) TP465 polypeptide and TP65 polypeptide, i) the molar ratio of TP465 to E1 / E2 heterodimer is 5:1 to 10:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) E1 / E2 heterodimer and b) TP465 polypeptide and TP65 polypeptide, i) the molar ratio of TP465 to E1 / E2 heterodimer is 10:1 to 25:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 10:1 to 25:1.As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 3:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 9:1, and ii) the molar ratio of TP65 to the E1 / E2 heterodimer is 9:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.1:1, and ii) the molar ratio of TP65 to the E1 / E2 heterodimer is 0.1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.3:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 0.3:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.5:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 0.5:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, wherein i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP65 to E1 / E2 heterodimer is 9:1.As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP65 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 9: 1, and ii) the molar ratio of TP65 to the E1 / E2 heterodimer is 3: 1. The amino acid sequences of the TP465 polypeptide and the TP65 polypeptide are provided above.

[0272] As a non-limiting example, in some cases, an immunogenic composition of the disclosure comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of the T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is, each independently, about 0.1:1 to about 25:1. As an example, in some cases, an immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide ("TP465") and a TP156 polypeptide ("TP156"), wherein i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 0.1:1 to 0.5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 0.5:1 to 1:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1 to 5:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 5:1 to 10:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 10:1 to 25:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 10:1 to 25:1.As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 1:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 1:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 3:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 9:1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 9:1. As another example, in some cases, the immunogenic composition of the disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.1:1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 0.1:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.3:1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 0.3:1. As another example, in some cases, the immunogenic composition of the present disclosure comprises a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 0.5:1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 0.5:1. As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, wherein i) the molar ratio of TP465 to E1 / E2 heterodimer is 3:1, and ii) the molar ratio of TP156 to E1 / E2 heterodimer is 9:1.As another example, in some cases, the immunogenic compositions of the disclosure comprise a) an E1 / E2 heterodimer and b) a TP465 polypeptide and a TP156 polypeptide, where i) the molar ratio of TP465 to the E1 / E2 heterodimer is 9: 1, and ii) the molar ratio of TP156 to the E1 / E2 heterodimer is 3: 1. The amino acid sequences of the TP465 polypeptide and the TP156 polypeptide are provided above.

[0273] The initial administration can be followed by a booster immunization with the same or a different immunogenic composition. In some examples, the subject methods of inducing an immune response include an initial administration of an immunogenic composition of the present disclosure, followed by at least one booster, and in some examples, two or more (e.g., three, four, or five) boosters. The interval between the initial administration and the booster, or between a given booster and a subsequent booster, can be from about 1 week to about 12 weeks, e.g., from about 1 week to about 2 weeks, from about 2 weeks to about 4 weeks, from about 4 weeks to about 6 weeks, from about 6 weeks to about 8 weeks, from about 8 weeks to about 10 weeks, or from about 10 weeks to about 12 weeks. The interval between the initial administration and the booster, or between a given booster and a subsequent booster, can be from 4 months to 6 months, or from 6 months to 1 year.

[0274] In some cases, a first dose of an immunogenic composition of the disclosure is administered at a first time and the administration is intramuscular, a second dose of an immunogenic composition of the disclosure is administered at a second time and the administration is intranasal, and a third dose of an immunogenic composition of the disclosure is administered at a third time and the administration is intranasal. In some cases, the second dose ("first booster") is administered about 1 week to about 12 weeks, e.g., about 1 week to about 2 weeks, about 2 weeks to about 4 weeks, about 4 weeks to about 6 weeks, about 6 weeks to about 8 weeks, about 8 weeks to about 10 weeks, about 10 weeks to about 12 weeks, 4 months to 6 months, or 6 months to 1 year, after the first dose. In some cases, the third dose (a "second booster") is administered about 1 week to about 12 weeks, e.g., about 1 week to about 2 weeks, about 2 weeks to about 4 weeks, about 4 weeks to about 6 weeks, about 6 weeks to about 8 weeks, about 8 weeks to about 10 weeks, about 10 weeks to about 12 weeks, 4 months to 6 months, or 6 months to 1 year, after the second dose.

[0275] In general, immunization can be achieved by administration of the immunogenic compositions of the present disclosure by any suitable route, including oral, nasal (e.g., intranasally), nasopharyngeal, parenteral, intestinal, gastric, topical, transdermal, subcutaneous, intramuscular, or intradermal administration of the compositions. In some cases, the immunogenic compositions of the present disclosure are administered intramuscularly. In some cases, the immunogenic compositions of the present disclosure are administered subcutaneously. Immunization can be achieved by local or systemic administration of the immunogenic compositions of the present disclosure in tablet, solid, powdered, liquid, or aerosol form, with or without added excipients. The immunogenic compositions of the present disclosure are often in liquid form. Actual methods for preparing parenterally administrable compositions are known or apparent to those skilled in the art and are described in more detail in publications such as Remington's Pharmaceutical Science, 15th ed., Mack Publishing Company, Easton, Pa. (1980). In some examples, immunization is accomplished by intramuscular injection of an immunogenic composition of the disclosure.

[0276] Suitable subjects for administration Individuals suitable for administration with the immunogenic compositions of the present disclosure include immunologically naive individuals (e.g., individuals who have never been infected with HCV and / or individuals who have never been administered an HCV vaccine). Individuals suitable for administration include humans.

[0277] Individuals suitable for administration with the immunogenic compositions of the disclosed compositions of the present disclosure include individuals who are at greater risk than the general population of becoming infected with HCV, including, for example, intravenous drug users, individuals who are recipients or prospective recipients of blood or blood products from another (donor) individual(s), individuals who are recipients or prospective recipients of non-autologous cells, tissues or organs from another (donor) individual, medical personnel, emergency medical personnel and non-medical personnel (e.g., first responders, firefighters, emergency medical team workers, etc.), etc.

[0278] Individuals suitable for administration with the immunogenic compositions of the disclosed compositions of the present disclosure include individuals who have recently become exposed to or infected with HCV. For example, the subject immunogenic compositions can be administered to an individual within about 24 hours to about 48 hours, about 48 hours to about 1 week, or about 1 week to about 4 weeks after potential or suspected exposure to HCV or infection by HCV.

[0279] Individuals suitable for administration with the immunogenic compositions of the present disclosure include individuals previously infected with HCV, individuals who have been treated for HCV, and individuals who have been cured.

[0280] Individuals suitable for administration with the immunogenic composition of the disclosed composition of the present disclosure include individuals who have been diagnosed with HCV infection, including individuals who are chronically infected. In some cases, individuals who have been diagnosed with HCV infection are treated with an antiviral agent and the immunogenic composition of the present disclosure. Suitable antiviral agents for treating HCV infection include, for example, ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide), interferon-alpha (IFN-α) ("IFN-α" includes IFN-α2a, IFN-α2b, IFN-α conjugated with poly(ethylene glycol) ("pegylated IFN-α"), where pegylated IFN-α can be pegylated IFN-α2a or pegylated IFN-α2b), HCV NS3 protease inhibitors (e.g., boceprevir, telaprevir) and HCV NS5 protease inhibitors.

[0281] In some cases, individuals diagnosed with HCV infection are treated with, for example, 1) IFN-α+ribavirin and the immunogenic composition of the present disclosure, 2) IFN-α+ribavirin+HCV protease inhibitor (e.g., boceprevir or telaprevir) and the immunogenic composition of the present disclosure, 3) Harvoni and the immunogenic composition of the present disclosure, 4) an inhibitor of HCV NS5B and the immunogenic composition of the present disclosure, 5) an inhibitor of HCV NS5A and the immunogenic composition of the present disclosure, or 6) an inhibitor of HCV NS5B+an inhibitor of HCV NS5A and the immunogenic composition of the present disclosure. Suitable antiviral agents for treating HCV infection include Sovaldi (sofosbuvir; a nucleotide analogue that functions as an NS5B polymerase inhibitor) and Harvoni, alone or in combination with pegylated IFN-α and ribavirin. Harvoni is a formulation containing 90 mg ledipasvir and 400 mg sovosbuvir. Ledipasvir is an inhibitor of HCV NS5A.

[0282] Examples of Non-Limiting Aspects of the Disclosure The above aspects, including the embodiments of the subject matter, may be beneficial alone or in combination with one or more other aspects or embodiments. Without limiting the above, certain non-limiting aspects of the present disclosure are provided below. As will be apparent to one of skill in the art upon reading this disclosure, each of the individually numbered aspects may be used or combined with any of the above or below individually numbered aspects. This is intended to provide support for all such aspect combinations, and is not limited to the aspect combinations explicitly provided below:

[0283] Aspect 1.

[0284] a1) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, wherein the T cell epitope polypeptides are

[0285] i) comprising the amino acid sequence: KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), where Xi is A or V, X2 is A or V, X3 is A or S, X4 is K or N, X5 is A or S, X6 is Y or F, X7 is M or L, and X8 is K or R;

[0286] TP35-NS3 T cell epitope polypeptide having a length of 35 amino acids;

[0287] ii) Amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13PGYP (SEQ ID NO: 80), where X1 is L or V, X2 is A or G, X3 is T or S, X4 is P or R, X5 is A or D, X6 is R or A, X7 is R, Q or S, X8 is S or P, X9 is E, T or Q, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 is Q or K),

[0288] iii) comprising the amino acid sequence: X1X2X3X4KGGRHLIFCHSKKKCDEX5AX6X7LX8 (SEQ ID NO: 94), where X1 is L or I, X2 is E, A, S, V or Q, X3 is Q, T, Y, F or L, X4 is I or L, X5 is L or I, X6 is A, K or S, X7 is K, Q or A, and X8 is T, R or S;

[0289] a TP27 T cell epitope polypeptide having a length of 27 amino acids, and

[0290] iv) Amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19 X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I, and X 11is P, T, A or Q, and X 12 is E or D, and X 13 is S, T or D, and X 14 is S or A, and X 15 is A, Q, R or K, and X 16 is R, K or X, and X 17 is T or M, and X 18 is Q, A, T or G, and X 19 is I, L or V), and having a length of 48 amino acids. and a fusion polypeptide comprising one or more T cell epitope polypeptides or two or more T cell epitope polypeptides selected from

[0291] b1) a second generation lipid adjuvant (SLA) that is a toll-like receptor 4 (TLR4) agonist formulated in i) a stable emulsion or ii) a liposomal composition containing saponin; or

[0292] a2) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, wherein the T cell epitope polypeptides are

[0293] i) a TP65 polypeptide comprising the amino acid sequence: TPIDTTIMAKNEVFCVDPX6KGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGX7SYGFQYS (SEQ ID NO: 152), where X6 is E, T or V and X7 is S, A or P, and having a length of 65 amino acids;

[0294] ii) Amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13PGYP (SEQ ID NO: 80), where X1 is L or V, X2 is A or G, X3 is T or S, X4 is P or R, X5 is A or D, X6 is R or A, X7 is R, Q or S, X8 is S or P, X9 is E, T or Q, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 is Q or K,

[0295] TP50C T cell epitope polypeptide having a length of 50 amino acids;

[0296] iii) a TP240 T cell epitope polypeptide comprising the amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSX1DATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGX2EGEIPFYGKAIPLX3X4IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTX5GDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 156), wherein X1 is T, V or Q, X2 is T, N, Q, H or S, X3 is E, S or A, X4 is V, T, Y, F or L, and X5 is S, Q or T;

[0297] iv) Amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I, and X 11 is P, T, A or Q, and X 12 is E or D, and X 13 is S, T or D, and X 14 is S or A, and X 15 is A, Q, R or K, and X 16 is R, K or X, and X 17 is T or M, and X 18 is Q, A, T or G, and X 19 is I, L or V), and having a length of 48 amino acids. and a fusion polypeptide comprising one or more T cell epitope polypeptides or two or more T cell epitope polypeptides selected from

[0298] b2) a second generation lipid adjuvant (SLA) which is a toll-like receptor 4 (TLR4) agonist formulated in i) a stable emulsion or ii) a liposomal composition containing saponin;

[0299] or,

[0300] a3) one or more T cell epitope polypeptides or a fusion polypeptide comprising two or more T cell epitope polypeptides, wherein the T cell epitope polypeptides are i) a TP35-NS3 T cell epitope polypeptide comprising the amino acid sequence: KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), where X1 is A or V, X2 is A or V, X3 is A or S, X4 is K or N, X5 is A or S, X6 is Y or F, X7 is M or L, and X8 is K or R, and having a length of 35 amino acids; ii) Amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), where X1 is L or V, X2 is A or G, X3 is T or S, X4 is P or R, X5 is A or D, X6 is R or A, X7 is R, Q or S, X8 is S or P, X9 is E, T or Q, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 is Q or K), iii) a TP27 T-cell epitope polypeptide comprising the amino acid sequence: X1X2X3X4KGGRHLIFCHSKKKCDEX5AX6X7LX8 (SEQ ID NO: 94), wherein X1 is L or I, X2 is E, A, S, V or Q, X3 is Q, T, Y, F or L, X4 is I or L, X5 is L or I, X6 is A, K or S, X7 is K, Q or A, and X8 is T, R or S, and having a length of 27 amino acids; iv) Amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X15 X 16 VX 17 X 18 X 19 X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I, and X 11 is P, T, A or Q, and X 12 is E or D, and X 13 is S, T or D, and X 14 is S or A, and X 15 is A, Q, R or K, and X 16 is R, K or X, and X 17 is T or M, and X 18 is Q, A, T or G, and X 19 is I, L or V), v) a TP240 T cell epitope polypeptide having a length of 240 amino acids, comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% amino acid sequence identity to the sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 157); vi) a TP65 T cell epitope polypeptide having a length of 65 amino acids, comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% amino acid sequence identity to the sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153); vii) A TP156 T cell epitope polypeptide having a length of 156 amino acids, comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% amino acid sequence identity to the sequence: KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160);

[0301] viii) a TP465 T cell epitope polypeptide comprising an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% amino acid sequence identity to an amino acid sequence depicted in any one of Figures 11A-11C, and having a length of 465 amino acids;

[0302] ix) a TP23 T cell epitope polypeptide comprising the amino acid sequence: DVVVX1X2TDALMTGX3TGDFDSVID (SEQ ID NO: 89), where X1 is V or C, X2 is A or S, and X3 is F or Y, and having a length of 23 amino acids;

[0303] x) Amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10(SEQ ID NO: 105) (wherein X1 is I or V, X2 is L or I, X3 is R or K, X4 is V, I or T, X5 is P, Q or T, X6 is G, A or S, X7 is A or V, X8 is V or T, X9 is S or A, and X 10 is V or I), and having a length of 35 amino acids;

[0304] xi) Amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX 12 X 13 (SEQ ID NO: 112) (wherein X1 is G, P or S, X2 is T, N, Q, H or S, X3 is E, T or D, X4 is K or R, X5 is L or I, X6 is E, A, S or Q, X7 is Q, T, Y, F or L, X8 is I or L, X9 is L or I, and X 10 is A, K or S, and X 11 is K, Q or A, and X 12 is T, R or S, and X 13 is G or S), and having a length of 42 amino acids;

[0305] xii) Amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 11 TGDFDSVIDX 12 X 13 X 14 (SEQ ID NO: 129) (wherein X1 is L or V, X2 is N or T, X3 is Y or F, X4 is L or V, X5 is S or A, X6 is V or I, X7 is T or A, X8 is S, Q or T, X9 is V or C, and X 10 is A or S, and X 11is F or Y, and X 12 is C or K, and X 13 is N or K, and X 14 is V or K), and having a length of 45 amino acids;

[0306] xiii) a TP33 T cell epitope polypeptide comprising the amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), where X1 is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and having a length of 33 amino acids;

[0307] xiv) a TP42-2 polypeptide comprising the amino acid sequence: KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), where X1 is A or S, X2 is K or A, X3 is V, S, R or T, X4 is A or G, X5 is L or M, X6 is I, L or V, and X7 is V or I, and having a length of 42 amino acids;

[0308] xv) a TP29 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP29 amino acid sequence depicted in FIG. 12 and having a length of 29 amino acids;

[0309] xvi) a TP50-NS2 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP50-NS2 amino acid sequence depicted in Figure 12 and having a length of 50 amino acids;

[0310] xvii) a TP52 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP25 amino acid sequence depicted in Figure 12 and having a length of 52 amino acids;

[0311] xviii) a TP70 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP70 amino acid sequence depicted in Figure 12 and having a length of 70 amino acids;

[0312] xix) a TP100 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP100 amino acid sequence depicted in FIG. 12 and having a length of 100 amino acids;

[0313] xx) a TP171 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP171 amino acid sequence depicted in FIG. 12 and having a length of 171 amino acids;

[0314] xxi) a TP228 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP228 amino acid sequence depicted in Figure 12 and having a length of 228 amino acids;

[0315] xxii) a TP553 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP553 amino acid sequence depicted in Figure 12 and having a length of 553 amino acids;

[0316] xxiii) a TP778 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP778 amino acid sequence depicted in Figure 12 and having a length of 778 amino acids; and

[0317] xxiv) a TP1987 polypeptide comprising an amino acid sequence having at least 50% amino acid sequence identity to the TP1987 amino acid sequence depicted in FIG. 12 and having a length of 1987 amino acids. and a fusion polypeptide comprising one or more T cell epitope polypeptides or two or more T cell epitope polypeptides selected from

[0318] b3) a second generation lipid adjuvant (SLA) which is a toll-like receptor 4 (TLR4) agonist formulated in i) a stable emulsion or ii) a liposomal composition containing saponin; 20. An immunogenic composition comprising:

[0319] Aspect 2. The SLA has the following structure: [ka] The immunogenic composition of embodiment 1, comprising:

[0320] Embodiment 3. The immunogenic composition of embodiment 1 or embodiment 2, wherein the liposome composition comprising saponin comprises a sterol.

[0321] Embodiment 4. The immunogenic composition of embodiment 3, wherein the saponin is complexed with a sterol.

[0322] Embodiment 5. The immunogenic composition of embodiment 3 or embodiment 4, wherein the sterol is cholesterol.

[0323] Embodiment 6 The immunogenic composition of any one of Embodiments 1-5, wherein the liposome composition comprises a phospholipid.

[0324] Embodiment 7. The immunogenic composition of embodiment 6, wherein the phospholipid is selected from the group consisting of DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DLPG, DMPG, DPPG, DSPG, DOPG, DSTAP, DPTAP, DSPE, DPPE, DMPE and DLPE.

[0325] Embodiment 8. The immunogenic composition of any one of embodiments 1 to 7, wherein the saponin is QS21, QS17, QS7, synthetic QS21 (SQS21), Quil-A, QS21-Api and QS21-Xyl.

[0326] Embodiment 9. The immunogenic composition of embodiment 1 or embodiment 2, wherein the stable oil-in-water emulsion comprises an aqueous phase and an oil phase, wherein the aqueous phase comprises SLA and the oil phase comprises squalene, wherein the squalene is present in the emulsion at a concentration of about 0.01% to about 1% v / v, and wherein the hydrophobic:lipophilic balance of the emulsion is greater than about 9.

[0327] Embodiment 10. The immunogenic composition of embodiment 9, wherein the aqueous phase comprises poloxamer 188 and glycerol.

[0328] Embodiment 11. The immunogenic composition of embodiment 9 or embodiment 10, wherein the oil phase comprises egg phosphatidylcholine or dimyristoylphosphatidylcholine (DMPC) or DOPC.

[0329] Embodiment 12 The immunogenic composition of any one of embodiments 9 to 11, comprising a surfactant.

[0330] Embodiment 13 The immunogenic composition of embodiment 12, wherein the surfactant is Pluronic F68.

[0331] Embodiment 14. a) the TP35-NS3 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79);

[0332] b) the TP50C T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87);

[0333] c) the TP27 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103);

[0334] d) the TP48 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136);

[0335] The immunogenic composition of any one of aspects 1 to 13.

[0336] 15. A fusion polypeptide comprising, in order from N-terminus to C-terminus:

[0337] a) TP35-NS3 T cell epitope polypeptide,

[0338] b) TP27 T cell epitope polypeptide;

[0339] c) a TP48 T cell epitope polypeptide, and

[0340] d) TP50C T cell epitope polypeptide 14. The immunogenic composition of any one of embodiments 1 to 13, comprising:

[0341] Embodiment 16 The immunogenic composition of any one of embodiments 1 to 15, comprising a Hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer polypeptide.

[0342] Embodiment 17 The immunogenic composition of embodiment 16, wherein the HCV E1 and / or E2 polypeptide is derived from HCV genotype 1.

[0343] Embodiment 18 The immunogenic composition of embodiment 16, wherein the HCV E1 and / or E2 polypeptide is derived from HCV genotype 2.

[0344] Embodiment 19 The immunogenic composition of embodiment 16, wherein the HCV E1 and / or E2 polypeptide is derived from HCV genotype 3.

[0345] Embodiment 20. The immunogenic composition of embodiment 16, wherein the HCV E1 and / or E2 polypeptides are derived from a) HCV genotypes 1, 2 and 3, b) HCV genotypes 1a, 2 and 3, c) HCV genotypes 1b, 2 and 3, d) HCV genotypes 1a, 1b, 2 and 3 or e) HCV genotypes 1 and 3.

[0346] Embodiment 21. The immunogenic composition of any one of embodiments 16 to 20, comprising an HCV E1 / E2 heterodimeric polypeptide and one or more T cell epitope polypeptides.

[0347] Embodiment 22. The immunogenic composition of embodiment 21, wherein the molar ratio of the one or more T-cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is from 0.1:1 to 25:1.

[0348] Embodiment 23. The immunogenic composition of embodiment 21, wherein the composition comprises two or more T cell epitope polypeptides, and the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently from 0.1:1 to 25:1.

[0349] Embodiment 24. The immunogenic composition of embodiment 23, wherein the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently from 2:1 to 15:1.

[0350] Embodiment 25. The immunogenic composition of embodiment 23, wherein the composition comprises four T cell epitope polypeptides, and the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently from 0.1:1 to 25:1.

[0351] Embodiment 26. The immunogenic composition of embodiment 25, wherein the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0.1:1 to 0.5:1, 0.5:1 to 1:1, 1:1 to 5:1, 5:1 to 10:1, or 10:1 to 25:1.

[0352] Embodiment 27. The immunogenic composition of embodiment 25, wherein the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0:1:1, 0.3:1, 0.5:1 or 1:1.

[0353] Embodiment 28. The immunogenic composition of embodiment 26, wherein the molar ratio of one or more of the four T-cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is 3:1.

[0354] Embodiment 29. The immunogenic composition of embodiment 26, wherein the molar ratio of one or more of the four T-cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is 9:1.

[0355] Embodiment 30. The immunogenic composition of any one of embodiments 25 to 29, wherein the four T cell epitope polypeptides are a TP50C polypeptide, a TP-35NS3 polypeptide, a TP27 polypeptide and a TP48 polypeptide.

[0356] 31. i) the TP50C polypeptide comprises the following amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87) and has a length of 50 amino acids;

[0357] ii) the TP35-NS3 polypeptide comprises the following amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79) and has a length of 35 amino acids;

[0358] iii) the TP27 polypeptide comprises the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103) and has a length of 27 amino acids;

[0359] iv) the TP48 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136);

[0360] The immunogenic composition of embodiment 30, having a length of 48 amino acids.

[0361] Embodiment 32. The immunogenic composition of embodiment 23, wherein the composition comprises two T cell epitope polypeptides, and the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently from 0.1:1 to 25:1.

[0362] Embodiment 33. The immunogenic composition of embodiment 32, wherein the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0.1:1 to 0.5:1, 0.5:1 to 1:1, 1:1 to 5:1, 5:1 to 10:1, or 10:1 to 25:1.

[0363] Embodiment 34. The immunogenic composition of embodiment 32, wherein the molar ratio of each of the two T-cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0:1:1, 0.3:1, 0.5:1 or 1:1.

[0364] Embodiment 35. The immunogenic composition of embodiment 32, wherein the molar ratio of one or more of the two T-cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is 3:1.

[0365] Embodiment 36. The immunogenic composition of embodiment 32, wherein the molar ratio of one or more of the two T-cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is 9:1.

[0366] 37. The two T cell epitope polypeptides

[0367] a) a TP465 polypeptide and a TP48 polypeptide,

[0368] b) a TP465 polypeptide and a TP65 polypeptide, or

[0369] c) TP465 polypeptide and TP156 polypeptide The immunogenic composition of any one of aspects 32 to 36,

[0370] Embodiment 38. The immunogenic composition of any one of embodiments 1 to 37, further comprising an adjuvant selected from MF59, alum, CpG oligonucleotides, cyclic dinucleotides, 3'-O-desacyl-4'-monophosphoryl lipid A (MPL), aluminum hydroxide, aluminum phosphate, AS01, AS02, AS03, AS04, 3M-052, and combinations thereof.

[0371] Embodiment 39. A method of inducing an immune response in an individual against Hepatitis C virus (HCV), comprising administering to the individual an effective amount of the composition of any one of embodiments 1-38.

[0372] Embodiment 40. a) administering a first dose of a composition at a first time; and

[0373] b) administering a second dose of the composition at a second time.

[0374] The method of embodiment 39, comprising:

[0375] Embodiment 41. The method of embodiment 40, wherein the second time is from about one week to about six months from the first time.

[0376] Embodiment 42 The method of any one of embodiments 39 to 41, wherein the administering is intramuscular administration.

[0377] Embodiment 43 The method of any one of embodiments 39 to 41, wherein the administering is subcutaneous administration.

[0378] Embodiment 44. A container comprising the immunogenic composition of any one of embodiments 1 to 38.

[0379] Embodiment 45. The container of embodiment 44, wherein the container and composition are sterile.

[0380] Embodiment 46. The container of embodiment 44 or embodiment 45, wherein the container is a syringe. EXAMPLES

[0381] The following examples are presented to provide those skilled in the art with a complete disclosure and description of how to make and use the invention, and are not intended to limit the scope of what the inventors regard as their invention, nor are they intended to represent that the following experiments are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.), but some experimental error and deviation should be accounted for. Unless otherwise indicated, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric. Standard abbreviations may be used, such as bp, base pair(s); kb, kilobase(s); pl, picoliter(s); s or sec, second(s); min, minute(s); h or hr, hour(s); aa, amino acid(s); kb, kilobase(s); bp, base pair(s); nt, nucleotide(s); im, intramuscular (intramuscularly); ip, intraperitoneal (intraperitoneally); sc, subcutaneous (subcutaneously); and the like.

[0382] Example 1 Here we report strong CD4 T cell and humoral responses to E1E2, as well as strong CD8 T cell and extremely robust CD4 T cell responses to the four TPs, when a mixture of E1E2 and the four TPs was adjuvanted with SLA-LSQ or with SLA-SE.

[0383] Experimental design and methods CB6-F1 mice were immunized intramuscularly with a mixture of E1E2 and four TPs (including TP50-C, TP35-NS3, TP27 and TP48) adjuvanted with (i) Alum-OH / MPLA (InvivoGen; San Diego, CA 92121 USA), (ii) AddaAS03 (InvivoGen), (iii) SLA-LSQ (IDRI) or (iv) SLA-SE (IDRI). Three injections were applied on days 0, 14 and 42 and mice were euthanized on day 56. Blood was collected on day 0 (before immunization) and day 56 (2 weeks after the third immunization). Serum was extracted, inactivated, stored and used for E1E2-specific enzyme-linked immunosorbent assay (ELISA) and neutralization assay at appropriate times. Spleens were harvested on day 56 and splenocytes were isolated and used in intracellular cytokine assays as previously reported. Landi et al. (2017) Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP, a STING activator or archaeosomes. Vaccine 35(50): p. 6949-6956. Short peptides spanning E1E2 and the four TPs were chemically synthesized, assembled into two separate pools, and used to restimulate splenocytes in vitro.

[0384] The amino acid sequences of the four TPs were as follows:

[0385] TP50-C: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87),

[0386] TP35-NS3: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79),

[0387] TP27: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103),

[0388] TP48:ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (sequence number 136).

[0389] result To evaluate the humoral immunogenicity of the adjuvanted HCV rE1E2-4TP vaccine, we compared the levels of E1E2-specific IgG in mouse serum (Figure 5) and the neutralizing activity of diluted sera after vaccination against HCV pseudoparticles (Figure 6). Results showed comparable or superior efficacy of the IDRI adjuvants (SLA-LSQ and SLA-SE) when compared to Alum-OH / MPLA and AddaAS03.

[0390] FIG. 5. E1E2-specific IgG levels in post-vaccinated mouse sera collected on day 56 after subtraction of levels in pre-vaccinated mouse sera collected on day 0.

[0391] Figure 6. Diluted post-vaccination mouse serum collected on day 56 was used to neutralize HCV pseudoparticles expressing E1E2 (data are normalized to pre-vaccination mouse serum collected on day 0).

[0392] To evaluate T cell responses, we investigated the presence of polyfunctional T cells secreting IFN-γ, TNF-α and / or IL-2 after in vitro restimulation of splenocytes. Flow cytometry data showed that IDRI-adjuvanted vaccines induced robust and highly robust CD4 T cell responses against E1, E2 and the four TPs, respectively. Notably, IDRI adjuvanted induced strong 4TP-specific CD8 T cell responses in preclinical animal studies (Figures 7A-7B). CD8 + T cells secreted both IFN-γ and TNF-α (Figure 7A). +T cells produced all three cytokines (IFN-γ, TNF-α, and IL-2) in pairwise combinations of IFN-γ and TNF-α (FIG. 7A) and IFN-γ and IL-2 (FIG. 7B). The data show that HCV vaccines, when adjuvanted with SLA-LSQ or SLA-SE, can induce both humoral and cellular immune responses as well as potent CD8 T cell responses.

[0393] Figure 7A-7B. E1E2-4TP mixtures adjuvanted with SLA-LSQ and SLA-SE inhibited CD8 T cells producing IFN-γ and TNF-α (Figure 7A). + T cells and CD4 cells producing IFN-γ, TNF-α, and IL-2 + It can induce the generation of T cells (Figures 7A and 7B).

[0394] Example 2 Method & Materials CB6-F1 mice were immunized intramuscularly with a mixture of adjuvanted E1E2 and TP (same four TPs as in Example 1). Three injections were administered on days 0, 14 and 42. Mice were euthanized on day 56 and spleens were harvested. In this experiment, splenocytes from mice vaccinated with antigen (E1E2-4TP) or antigen adjuvanted with SLA-LSQ or SLA-SE were stimulated in vitro with full-length individual TPs instead of peptide pools containing short peptides spanning all four TPs. The presence of polyfunctional T cells expressing IFN-γ, TNF-α and / or IL-2 was investigated in an intracellular cytokine assay using flow cytometry.

[0395] result The data are presented in Figures 13A-13B. Flow cytometry data show that restimulation of splenocytes with TP48 induced highly potent CD4+ T cells in mice receiving the adjuvanted vaccine. +Figure 13 shows that TP48 induces CD4 T cell responses in the SLA-SE group. This response is the highest among TPs, followed by TP35-NS3, TP50-C, and finally TP27. Among TPs, TP27 induced CD4 T cell responses in the SLA-SE group. Polyfunctional CD4 T cells were able to produce all three cytokines in pairwise combinations of IFN-γ and TNF-α (Figure 13A) and IFN-γ and IL-2 (Figure 13B). With regard to CD8 T cells, TP48 is a polyfunctional CD8 T cell that expresses both IFN-γ and TNF-α (Figure 14A) but not IL-2 (Figure 14B). + This HCV vaccine contains both humoral and cellular components and can induce strong CD8 T cell responses when adjuvanted with SLA-LSQ or SLA-SE.

[0396] Although the present invention has been described with reference to specific embodiments thereof, it should be understood by those skilled in the art that various modifications may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular condition, material, composition, process, process step(s) to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims

1. a) A fusion polypeptide comprising one or more T cell epitope polypeptides, or two or more T cell epitope polypeptides, wherein the T cell epitope polypeptide is i) Amino acid sequence: KSTKVPX 1 AYX 2 X 3 QGYX 4 VLVLNPSVAATLGFGX 5 X 6 X 7 SX 8 (SEQ ID NO: 73) (where X 1 is A or V, X 2 is A or V, X 3 is A or S, X 4 is K or N, X 5 is A or S, X 6 is Y or F, X 7 is M or L, X 8 is K or R), and a TP35-NS3 T cell epitope polypeptide having a length of 35 amino acids ii) Amino acid sequence: GVYX 1 LPRRGPRLGVRX 2 TRKX 3 SERSQPRGRRQX 4 IPKX 5 X 6 X 7 X 8 X 9 GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80) (where X 1 is L or V, X 2 is A or G, and X 3 is T or S, X 4 is P or R, X 5 is A or D, and X 6 is R or A, X 7 is R, Q, or S, and X 8 is S or P, X 9 is E, T, or Q, and X 10 is R or K, and X 11 is S, T, H or A, and X 12 is A or G, and X 13 TP50C T cell epitope polypeptide, which contains Q or K and has a length of 50 amino acids, iii) Amino acid sequence: X 1 X 2 X 3 X 4 KGGRHLIFCHSKKKCDEX 5 AX 6 X 7 LX 8 (Sequence No. 94) (where X 1 is L or I, and X 2 is E, A, S, V or Q, and X 3 is Q, T, Y, F or L, and X 4 is I or L, X 5 is L or I, and X 6 is A, K, or S, and X 7 is K, Q or A, and X 8 TP27 T cell epitope polypeptide, which contains (T, R, or S) and has a length of 27 amino acids, and iv) Amino acid sequence: X 1 X 2 X 3 RHX 4 GX 5 X 6 EGX 7 X 8 QWMNRLIAFASRGNHVX 9 PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19 L (SEQ ID NO: 134) (where X 1 is I or V, X 2 is L or I, X 3 is R or K, X 4 is V, I or T, X 5 is P, Q or T, X 6 is G, A or S, X 7 is A or V, X 8 is V or T, X 9 is S or A, X 10 is V or I, X 11 is P, T, A or Q, X 12 is E or D, X 13 is S, T or D, X 14 is S or A, X 15 is A, Q, R or K, X 16 is R, K or X, X 17 is T or M, X 18 is Q, A, T or G, and X 19 is I, L or V), and has a length of 48 amino acids, a TP48 T cell epitope polypeptide v) TP240 T cell epitope polypeptide having a length of 240 amino acids and containing an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity to sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (Sequence ID 157), vi) TP65 T cell epitope polypeptide having a length of 65 amino acids and containing an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with respect to sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153), vii) A TP156 T cell epitope polypeptide having a length of 156 amino acids and containing an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity to the sequence: KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), and viii) TP465 T cell epitope polypeptide having a length of 465 amino acids and containing an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with respect to any one of the amino acid sequences shown in Figures 11A to 11C. A fusion polypeptide comprising one or more T cell epitope polypeptides or two or more T cell epitope polypeptides, selected from the above, and b) i) Second-generation lipid adjuvants (SLAs) that are Toll-like receptor 4 (TLR4) agonists formulated in a stable emulsion or ii) a liposome composition containing saponins. An immunogenic composition containing [the specified substance].

2. The aforementioned SLA has the following structure: 【Chemistry 1】 The immunogenic composition according to claim 1, having the following characteristics.

3. The liposome composition containing saponins contains sterols, preferably a) The saponin forms a complex with the sterol, and / or b) The sterol is cholesterol, and / or c) The liposome composition comprises a phospholipid, preferably selected from the group consisting of DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DLPG, DMPG, DPPG, DSPG, DOPG, DSTAP, DPTAP, DSPE, DPPE, DMPE and DLPE, and / or d) The immunogenic composition according to claim 1, wherein the saponin is QS21, QS17, QS7, synthetic QS21 (SQS21), Quil-A, QS21-Api, and QS21-Xyl.

4. The stable oil-in-water emulsion comprises an aqueous phase and an oil phase, wherein the aqueous phase comprises the SLA, the oil phase comprises squalene, the squalene is present in the emulsion at a concentration of about 0.01% to about 1% v / v, and the hydrophobic:lipophilic balance of the emulsion is greater than about 9, preferably a) The aqueous phase comprises poloxamer 188 and glycerol, and / or b) The oil phase contains egg phosphatidylcholine or dimyristoyl phosphatidylcholine (DMPC), The immunogenic composition according to claim 1.

5. The immunogenic composition according to claim 4, comprising a surfactant, preferably the surfactant being Pluronic F68.

6. A) The composition comprises TP35-NS3 T cell epitope polypeptide, TP50C T cell epitope polypeptide, TP27 T cell epitope polypeptide, and TP48 T cell epitope polypeptide, i) The TP35-NS3 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79), ii) The TP50C T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87), iii) The TP27 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103), iv) The TP48 T cell epitope polypeptide contains an amino acid sequence that has at least 80% amino acid sequence identity with the amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), or B) The composition comprises TP156 T cell epitope polypeptide, TP465 T cell epitope polypeptide, TP48 T cell epitope polypeptide, and TP65 T cell epitope polypeptide, i) The TP156 T cell epitope polypeptide comprises an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with the sequence: KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), and the TP156 T cell epitope polypeptide has a length of 156 amino acids. ii) The TP465 T cell epitope polypeptide comprises an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with respect to any one of the amino acid sequences shown in Figures 11A to 11C, and the TP465 T cell epitope polypeptide has a length of 465 amino acids, iii) The TP48 T cell epitope polypeptide comprises an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with the amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), and the TP48 T cell epitope polypeptide has a length of 48 amino acids, and iv) The TP65 T cell epitope polypeptide comprises an amino acid sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% amino acid sequence identity with the sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153), and the TP65 T cell epitope polypeptide has a length of 65 amino acids. The immunogenic composition according to any one of claims 1 to 5.

7. The aforementioned fusion polypeptide is arranged in the order from the N-terminus to the C-terminus. a) The TP35-NS3 T cell epitope polypeptide, b) The TP27 T cell epitope polypeptide, c) The TP48 T cell epitope polypeptide, and d) The TP50C T cell epitope polypeptide An immunogenic composition according to any one of claims 1 to 5, comprising:

8. An immunogenic composition according to any one of claims 1 to 5, comprising hepatitis C virus (HCV) E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer polypeptide, preferably the HCV E1 / E2 heterodimer polypeptide, HCV E1 polypeptide, or HCV E2 polypeptide derived from HCV genotype 1, 2, or 3.

9. The immunogenic composition according to claim 8, comprising an HCV E1 / E2 heterodimer polypeptide and one or more T cell epitope polypeptides, preferably having a molar ratio of 0.1:1 to 25:1 between the one or more T cell epitope polypeptides and the HCV E1 / E2 heterodimer polypeptide.

10. The immunogenic composition according to claim 9, wherein the composition comprises two or more T cell epitope polypeptides, and the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0.1:1 to 25:

1.

11. The composition comprises four T cell epitope polypeptides, a) The molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is independently 0.1:1 to 25:1, 0.1:1 to 0.5:1, 0.5:1 to 1:1, 1:1 to 5:1, 5:1 to 10:1, or 10:1 to 25:1, or b) The molar ratio of one or more of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is 3:1 or 9:

1. The immunogenic composition according to claim 10.

12. The immunogenic composition according to claim 11, wherein the four T cell epitope polypeptides are TP50C polypeptide, TP-35NS3 polypeptide, TP27 polypeptide, and TP48 polypeptide.

13. An immunogenic composition according to any one of claims 1 to 5, further comprising MF59, alum, CpG oligonucleotide, cyclic dinucleotide, 3'-O-desacyl-4'-monophosphoryllipid A (MPL), aluminum hydroxide, aluminum phosphate, AS01, AS02, AS03, AS04, 3M-052, and an adjuvant selected from combinations thereof.

14. A composition according to any one of claims 1 to 5 for use in the treatment of hepatitis C virus (HCV), wherein the use comprises administering an effective amount of the composition to an individual to induce an immune response to hepatitis C virus (HCV).

15. A composition for use according to claim 14, a) The aforementioned use, i) Administering a first dose of the composition at a first time, and ii) administering a second dose of the composition at a second time, preferably the second time being a period of about one week to about six months from the first time, and / or b) The administration is i) intramuscular or ii) subcutaneous, composition.

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