Hepatitis C virus immunogenic compositions and methods of use thereof

Abstract

The present invention 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 invention provides a method of inducing an immune response in an individual against hepatitis C virus, the method comprising administering to the individual an immunogenic composition of the invention.

Description

[0001] Cross-references

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 324,339 filed on March 28, 2022, U.S. Provisional Patent Application No. 63 / 358,332 filed on July 5, 2022, and U.S. Provisional Patent Application No. 63 / 397,676 filed on August 12, 2022, all of which are incorporated herein by reference.

[0003] Incorporation by Reference of Electronically Submitted Materials

[0004] The Sequence Listing is provided as a Sequence Listing XML, which was created on March 26, 2023 and is 255,129 bytes in size. The entire contents of the Sequence Listing XML are incorporated herein by reference. Background Art

[0005] Hepatitis C virus (HCV) is a blood-borne pathogen that infects an estimated 150-200 million people worldwide. HCV infection can be asymptomatic and cleared by the patient, sometimes without medical intervention. However, most patients develop chronic HCV infection, which can lead to liver inflammation, scarring, and even liver failure or liver cancer. In the United States alone, more than 3 million people are chronically infected.

[0006] HCV virus particles contain a positive single-stranded RNA genome of about 9.5 kb. The genome encodes a single polyprotein of 3010 to 3030 amino acids. The structural proteins include the core protein that forms the viral nucleocapsid and two envelope glycoproteins E1 and E2.

[0007] There is a need in the art for compositions and methods for inducing an immune response against HCV. Summary of the invention

[0008] The present invention 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 invention provides a method for inducing an immune response against hepatitis C virus in an individual, the method comprising administering the immunogenic composition of the present invention to the individual. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figures 1A-1CProvide an amino acid sequence alignment of an example of the core-E1-E2 coding region of HCV genotype 1 virus (specifically, representative HCV 1A, 1B, and 1C genotypes). Use Geneious software v5.6.4 to align the Genbank database sequences of the coding region core-E1-E2. Number the amino acids according to strain NP_671941 (H77). Consensus sequence: 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.

[0010] Figure 2A-2CAn alignment of the amino acid sequences of the core-E1-E2 coding regions of representative HCV 2A and HCV2B subtypes is provided. The Genbank database sequences of the coding region core-E1-E2 were aligned using Geneious software v5.6.4. The amino acid numbers described are 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.

[0011] Figures 3A-3C Provided is an amino acid sequence alignment of the core E1-E2 coding regions of representative HCV 3A, 3B and 3K genotypes. The Genbank database sequences of the coding regions core-E1-E2 were aligned using Geneious software v5.6.4. Common sequence: 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.

[0012] Figure 4A-4BThe amino acid sequence of the core-E1-E2 coding region of HCV genotype 7a is provided. 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).

[0013] Figure 5 Describe the levels of HCV E1 / E2-specific IgG in the sera of mice after vaccination.

[0014] Figure 6 Neutralization of HCV pseudoparticles by sera from vaccinated mice is described.

[0015] Figure 7A-7B The data described show that the E1E2-4TP mixture adjuvanted with SLA-LSQ or SLA-SE can induce the generation of T cells producing IFN-γ, IL-2 and TNF-α.

[0016] Figures 8A-8B Describe the structures of several saponins.

[0017] Fig. 9 Describe the structures of squalene, miglyol 810, DOPC, Tween 80, and Pluronic F68.

[0018] Fig.10 The amino acid sequence of the TP fusion polypeptide is provided (SEQ ID NO: 57).

[0019] Figures 11A-11C Amino acid sequences of TP465 polypeptides are provided (SEQ ID NOs: 58-60, respectively).

[0020] Fig.12 Amino acid sequences of examples of T cell epitope polypeptides ("TPs") are provided (SEQ ID NOs: 61-70, respectively).

[0021] Figures 13A-13B The data described show that the E1E2-4TP mixture 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. + T cells.

[0022] Figures 14A-14B The data described show that when stimulated in vitro with individual TPs, the E1E2-4TP mixture adjuvanted with SLA-LSQ or SLA-SE can induce the generation of CD8 + T cells. DETAILED DESCRIPTION

[0023] definition

[0024] The term "hepatitis C virus" ("HCV") as used herein refers to any of the many different genotypes and isolates of hepatitis C virus. Thus, "HCV" encompasses any of the many genotypes, subtypes, or quasispecies 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 quasispecies. 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, type 1, type 1a, H77 type 1b, type 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.

[0025] 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.

[0026] As used herein, the term "isolated" refers to a polypeptide in an environment different from the environment in which the polypeptide naturally exists when referring to the polypeptide. An isolated polypeptide may be purified. "Purified" means that the compound of interest (e.g., polypeptide) has been separated from the components that accompany it in nature. "Purified" may also be used to refer to a polypeptide that is separated from components that may accompany it during the production of the polypeptide (e.g., in vitro synthesis, etc.). In some embodiments, when the polypeptide (or polypeptide mixture) is at least 60% or at least 75% by weight without organic molecules that are naturally associated with it or associated during the production process, the polypeptide (or polypeptide mixture) is substantially pure. In some cases, the purity of the polypeptide is 30% to 60%. In some cases, the purity of the polypeptide (or polypeptide mixture) is at least 60%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% by weight. For example, in some cases, an E1 or E2 polypeptide (or a mixture of E1 and E2 polypeptides, such as an E1 / E2 heterodimer) is substantially pure when the E1 or E2 polypeptide (or mixture of E1 and E2 polypeptides) is at least 60% or at least 75% free by weight of organic molecules that are naturally associated with the polypeptide or that are associated during production. In some cases, the purity of the E1 or E2 polypeptide (or 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% by weight. In some cases, if the composition comprises an E2 polypeptide, the purity of 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% by weight. In some cases, if the composition comprises an E1 / E2 heterodimer complex polypeptide, the purity of 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% by weight. In some cases, if the composition comprises a T cell epitope polypeptide, the purity of 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% by weight.

[0027] The terms "peptide", "polypeptide" and "protein" are used interchangeably herein and refer to a polymeric form of amino acids of any length, which may include coded and non-coded amino acids, chemically or biochemically modified or derivatized amino acids, and polypeptides with modified peptide backbones. The term "polypeptide" includes glycosylated polypeptides.

[0028] The term "heterologous" refers to two components defined by structures derived from different sources. For example, if "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, for example, an amino acid sequence that is naturally not operably linked to a polypeptide. As another example, if the composition comprises an HCV E1 / E2 heterodimer and a "heterologous" polypeptide, the "heterologous polypeptide" is a polypeptide other than HCV E1 or HCV E2. As another example, if the fusion polypeptide comprises: a) a T cell epitope polypeptide ("TP") and b) a heterologous fusion partner polypeptide, the "heterologous fusion partner polypeptide" is a polypeptide that is not found in nature to associate with a T cell epitope polypeptide. As another example, if "heterologous" is used in the context of a nucleic acid or nucleotide sequence, the operably linked nucleotide sequence included in the nucleic acid is not usually linked in nature. For example, an IRES can be heterologous to a nucleotide sequence encoding an HCV E1 and / or E2 polypeptide, wherein the IRES is from an organism other than HCV (e.g., a virus).

[0029] A "conservative amino acid substitution" is a substitution of one amino acid residue by another amino acid residue having a side chain (R group) of similar chemical properties (e.g., charge or hydrophobicity). Typically, conservative amino acid substitutions do not significantly change the functional properties of a protein. Where two or more amino acid sequences differ from one another due to conservative substitutions, the percentage of sequence identity or degree of similarity may be adjusted upward to correct for the conservative nature of the substitution. Means for making such adjustments are well known to those skilled in the art. See, e.g., Pearson (1994) Methods Mol. Biol. 24: 307-331, which is incorporated herein by reference. Examples of amino acid groups having side chains with similar chemical properties and thus constituting conservative amino acid substitution groups include: 1) amino acids containing aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) amino acids containing aliphatic hydroxyl side chains: serine and threonine; 3) amino acids having amide-containing side chains: asparagine and glutamine; 4) amino acids containing aromatic side chains: phenylalanine, tyrosine and tryptophan; 5) amino acids having basic side chains: lysine, arginine and histidine; 6) amino acids having acidic side chains: aspartic acid and glutamic acid, and 7) amino acids having sulfur-containing side chains: cysteine ​​and methionine. Examples of conservative amino acid substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamic acid-aspartic acid and asparagine-glutamine.

[0030] Before further describing the present invention, it should be understood that the present invention is not limited to the specific embodiments described, and therefore, may of course vary. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments and is not intended to be limiting, as the scope of the present invention will only be limited by the appended claims.

[0031] If a numerical range is provided, it is understood that unless the context clearly dictates otherwise, each intermediate value between the upper and lower limits of the range, to one-tenth of the unit of the lower limit, and any other specified value or intermediate value within the range are included in the present invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges, and are also encompassed in the present invention, subject to any explicitly excluded limit points within the range. If the range includes one or two limit points, the range excluding one or both of the limit points is also included in the present invention.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials cited in the publications.

[0033] It must 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, reference to "an HCV E1 polypeptide" includes a plurality of such polypeptides, and reference to "the QS21 molecule" includes reference to one or more QS21 molecules and equivalents thereof known to those skilled in the art, and so forth. It is also noted that the claims may be drafted to exclude any optional elements. Therefore, this statement is intended to serve as antecedent basis for use of the term "solely", "only", and the like in connection with reciting claim elements or using a "negative" limitation.

[0034] It will be appreciated that, for the sake of clarity, certain features of the invention described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, for the sake of brevity, various features of the invention described in the context of a single embodiment may also be provided individually or in any suitable sub-combination. All combinations of embodiments belonging to the invention are specifically included in the invention and disclosed herein, just as each combination is individually and explicitly disclosed. In addition, all sub-combinations of the various embodiments and elements thereof are also specifically included in the invention and disclosed herein, just as each such sub-combination is individually and explicitly disclosed herein.

[0035] The publications discussed herein are provided only because their disclosure precedes the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to be invented prior to such publications by virtue of priority. In addition, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed. DETAILED DESCRIPTION OF THE INVENTION

[0037] The present invention 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), which is a toll-like receptor 4 (TLR4) agonist, formulated in the following: i) a stable emulsion; or ii) a liposome composition comprising saponin. The present invention 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) hepatitis C virus (HCV) E1 and / or HCV E2 polypeptides; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposome composition comprising saponin. The present invention provides a method for inducing an immune response against HCV in an individual, the method comprising administering an effective amount of the immunogenic composition of the present invention to the individual.

[0038] As described above, in some cases, the immunogenic composition of the present invention comprises: one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; and HCV E1 and / or E2 polypeptides. HCV E1 and / or E2 polypeptides act as humoral elements (i.e., induce the production of neutralizing antibodies), and T cell epitope polypeptides (or fusion polypeptides comprising T cell epitope polypeptides) act to induce CD4 + and CD8 + It was found that including an adjuvant comprising SLA in the immunogenic composition (either in a liposomal composition comprising saponin or as a stable emulsion) can induce a strong CD4 + and CD8 + In particular, adjuvants containing SLA (either in a saponin-containing liposome composition or as a stable emulsion) induced more robust CD4 T cell responses than when Alum-OH / MPLA or AddaAS03 were used as adjuvants. + and CD8 + T cell response.

[0039] Immunogenic composition

[0040] The present invention 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) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. The present invention 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) HCV E1 and / or HCV E2 polypeptides; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0041] When administered to an individual, the immunogenic composition of the present invention can induce stronger CD4 Tg expression than a reference immunogenic composition comprising Alum-OH / MPLA or AS03 as an adjuvant. + T cell responses and / or stronger CD8 + T cell response, wherein the reference immunogenic composition comprises the same T cell epitope polypeptide or fusion polypeptide as the immunogenic composition of the invention, the fusion polypeptide comprising the T cell epitope polypeptide, or wherein the reference immunogenic composition comprises the same T cell epitope polypeptide or fusion polypeptide as the immunogenic composition of the invention (the fusion polypeptide comprising the T cell epitope polypeptide), and the same HCV E1 and / or E2 polypeptide. In other words, for comparison purposes, the reference immunogenic composition differs from the immunogenic composition of the invention only in the adjuvant included.

[0042] In some cases, the immunogenic compositions of the invention induce CD4 + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times, or more than 25 times higher. In some cases, the immunogenic compositions of the invention induce CD8 + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times, or more than 25 times higher. In some cases, the immunogenic compositions of the invention induce CD4 + T cell responses and CD8 + T cell response, the response being greater than that induced by the reference immunogenic composition + T cell responses and CD8 +The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times or more than 25 times higher.

[0043] For example, the immunogenic composition of the present invention comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposome composition comprising saponin, the immunogenic composition of the present invention can induce CD4 T cells against HCV. + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times or more than 25 times higher, wherein the reference immunogenic composition comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) Alum-OH / MPLA.

[0044] As another example, the immunogenic composition of the present invention comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposome composition comprising saponin, the immunogenic composition of the present invention can induce CD8 against HCV. + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times or more than 25 times higher, wherein the reference immunogenic composition comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) Alum-OH / MPLA.

[0045] As another example, the immunogenic composition of the present invention comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposome composition comprising saponin, the immunogenic composition of the present invention can induce CD4 T cells against HCV. + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times or more than 25 times higher, wherein the reference immunogenic composition comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) AS03.

[0046] As another example, the immunogenic composition of the present invention comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposome composition comprising saponin, the immunogenic composition of the present invention can induce CD8 against HCV. + T cell response, the response being greater than that induced by the reference immunogenic composition + The T cell response is at least 10%, at least 15%, at least 25%, at least 50%, at least 75%, at least 100% (or twice), at least 2.5 times, at least 5 times, at least 10 times, at least 25 times or more than 25 times higher, wherein the reference immunogenic composition comprises: a) one or more T cell epitope polypeptides, or a fusion polypeptide comprising two or more T cell epitope polypeptides; b) HCV E1 and / or HCV E2 polypeptides; and c) AS03.

[0047] Alum-OH / MPLA is an adjuvant comprising: a) aluminum hydroxide; and b) monophosphoryl lipid A (MPLA). AddaS03 TM It is an oil-in-water nanoemulsion adjuvant containing squalene, DL-α-tocopherol and polysorbate 80 AS03 is an oil-in-water emulsion containing 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.

[0048] Squalene has the following structure:

[0049]

[0050] Polysorbate 80 has the following structure:

[0051]

[0052] Liposome composition containing saponin (SLA-liposome composition)

[0053] As described above, in some cases, the immunogenic composition of the invention comprises SLA in a liposome composition comprising saponin. See, for example, US2020 / 0276299. SLA in a liposome composition comprising saponin is also referred to herein as "SLA-LSQ".

[0054] In some cases, the saponin is present in the liposomal composition at a concentration of about 1 μg per unit dose to about 10 μg per unit dose or about 1 μg per unit dose to about 8 μg per unit dose. In some cases, the unit dose is 0.5 mL.

[0055] In some cases, the weight ratio of SLA to saponin is about 2.5 to 1.

[0056] In some cases, the liposome composition comprising a 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.

[0057] The saponin can be present in the formulation at a concentration of about 2 μg / mL to about 8 μg / mL. In some cases, a unit dose of the SLA-liposome composition comprises 2 μg to 4 μg of saponin. In some cases, the unit dose is 0.5 mL.

[0058] SLA can 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.

[0059] In some cases, the SLA-liposome composition comprises: i) 20 μg / mL SLA; ii) 8 μg / mL QS-21; iii) cholesterol; and iv) dioleoylphosphatidylcholine; wherein QS21 and cholesterol are present in a weight:weight (w:w) ratio of 1:125. Dioleoylphosphatidylcholine and cholesterol may be present in a w:w ratio of 4:1.

[0060] The average diameter (i.e., number average diameter) of the liposome can be 1 micron or less. In some cases, the average particle diameter (i.e., number average diameter) of the liposome particles is about 900nm or less, about 800nm ​​or less, about 700nm or less, about 600nm or less, about 500nm or less, about 400nm or less, 300nm or less or 200nm or less, for example, about 50nm to about 900nm, about 50nm to about 800nm, about 50nm to about 700nm, about 50nm to about 600nm, about 50nm to about 500nm, about 50nm to about 400nm, about 50nm to about 300nm, about 50nm to about 200nm, about 50nm to about 175nm, about 50nm to about 150nm, about 50nm to about 125nm, about 50nm to about 100nm. The size of the liposomes 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.

[0061] Phospholipids

[0062] The SLA-liposome composition may comprise 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-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC); 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC); distearyltrimethylammonium propane (DSTAP); dipalmitoyl (C16:0) trimethylammonium propane (DPT AP); 1,2-distearoyl-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-phosphoglycerol (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-dioleoyl-sn-glycerol -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, DSPS1,2-distearoyl-sn-glycero-3-phospho-L-serine; DOPS: 1,2-dioleoyl-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'-inositol); DMPI: 1,2-myristoyl-sn-glycero-3-phospho-(1'-inositol); DPPI: 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-inositol); DSPI: 1,2-distearoyl-sn-glycero-3-phosphoinositol; DOPI: 1,2-dioleoyl-sn-glycero-3-phospho-(1'-inositol); and POPI: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoinositol.In some cases, 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.

[0063] Saponin

[0064] In some cases, the saponin is an immunologically active saponin fraction derived from the bark of Quillaja saponaria Molina. In some cases, the saponin is QS21.

[0065] QS21 has the following structure:

[0066]

[0067] 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.

[0068] like Fig. 8A As shown, naturally occurring QS-21 has: (i) a triterpene aglycone core, saponic acid; (ii) a branched trisaccharide linked to the C3 OH group of saponic acid via a β-glycosidic ether bond; and (iii) a linear tetrasaccharide linked to the C28 carboxyl group of saponic acid via a β-glycosidic ester bond. The reducing end of the C28 tetrasaccharide is a β-D-fucosyl unit, the 4-O position of which is terminated by a glycosylated pseudodimeric fatty acyl chain. QS-21 is a mixture of two isomeric disaccharide chain saponins. The two structural isomers of QS-21 differ in the non-reducing end of the C28 tetrasaccharide. One isomer, QS-21 api With terminal β-D-apiosyl unit; another isomer QS-21 xyl It has a terminal β-D-xylosyl unit.

[0069] In some cases, the saponin comprises Quil-A or a derivative thereof, such as QS7. Other suitable saponins include Escin, Digitonin, Gypsophila saponin, or Chenopodiumquinoa saponin. In some cases, the saponin comprises QS-7. In some cases, the saponin comprises QS-17. In some cases, the saponin comprises QS-18. The structures of QS-7, QS-17, and QS-18 are as shown in Figure 8B shown.

[0070] Stable emulsion

[0071] As described above, in some cases, the immunogenic compositions of the invention comprise 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).

[0072] In some cases, SLA-SE is an emulsion comprising: a) an aqueous phase comprising: i) ammonium phosphate buffer; ii) a detergent (e.g., Pluronic F68 or Tween 80); and iii) glycerol; and b) an oil phase comprising: i) SLA; ii) phosphatidylcholine (PC); and iii) squalene. Miglyol 810 can be used instead of squalene. In some cases, SLA-SE comprises 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as PC. In some cases, SLA-SE does not comprise an antioxidant. In some cases, SLA-SE does comprise an antioxidant, e.g., wherein the antioxidant is tocopherol (vitamin E). In some cases, the detergent is Pluronic F68.

[0073] 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 9-12). 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 comprises 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as the PC. In some cases, the emulsion comprises DOPC as the PC.

[0074] PC can be egg yolk PC, soybean PC, 1,2-dioleoyl-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-dipalmitoyl-sn-glycero-3-phosphocholine. In some cases, PC is DOPC.

[0075] The structures of squalene, miglyol 810, DOPC, Tween 80 and Pluronic F68 are as follows Fig. 9 shown.

[0076] In some cases, SLA-SE comprises: i) 10% weight / volume squalene; ii) 0.25 mg / mL SLA; iii) 0.5% weight / volume vitamin E; iv) glycerol; and v) PC.

[0077] In some cases, the SLA-SE includes the components listed in the following table.

[0078] Components Weight or volume % Concentration (mg / ml) Squalene 4.00%v / v 34.34 glycerin 0.720%v / v 9.09 PC 0.76%w / v 7.84 SLA 0.04%w / v 0.4 Pluronic F68 or Tween 80 0.036% or 0.21% s / v 0.36 or 2.13 25 mM ammonium phosphate buffer 95.28%v / v

[0079] TLR7 / 8 agonists

[0080] The present invention 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 invention provides immunogenic compositions comprising: a) a TLR 7 / 8 agonist; and b) a fusion polypeptide comprising two or more TPs. The present invention provides immunogenic compositions comprising: a) a TLR7 / 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 invention 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.

[0081] In some cases, the TLR 7 / 8 agonist is 3M-052 (also known as "Telratolimod" or "MEDI9197"). The 3M-052 adjuvant is an imidazoquinoline with an 18-C fatty acyl chain that imparts enhanced hydrophobicity, reduced systemic spread, and improved bioavailability. In some cases, 3M-052 is formulated with poly(lactic-co-glycolic acid) (PLGA). In some cases, 3M-052 is formulated with PLGA nanoparticles. In some cases, 3M-052 is formulated with alum.

[0082] 3M-052 has the following structure:

[0083]

[0084] Other adjuvants

[0085] The present invention provides immunogenic compositions comprising: a) one or more adjuvants; and b) one or more T cell epitope polypeptides (one or more "TPs"). The present invention provides immunogenic compositions comprising: a) one or more adjuvants; and b) a fusion polypeptide comprising two or more TPs. The present invention provides immunogenic compositions comprising: a) one or more adjuvants; b) one or more TPs; and c) HCV E1 polypeptides, HCV E2 polypeptides, or HCV E1 / E2 heterodimers. The present invention provides immunogenic compositions comprising: a) one or more adjuvants; b) a fusion polypeptide comprising two or more TPs; and c) HCV E1 polypeptides, HCV E2 polypeptides, or HCV E1 / E2 heterodimers. The one or more adjuvants may be one or more of the adjuvants listed below. In some cases, the one or more adjuvants include a combination of the adjuvants listed above (e.g., SLA-SE or SLA-LSQ) and one or more adjuvants listed below.

[0086] Suitable adjuvants include, for example, monophosphoryl lipid A (MPL), 3-Q-deacylated-4'-monophosphoryl lipid A (3DMPL), poly (D, L-lactide-co-glycolide) (PLG), 3M-052, MF59, AS03, AS04, AS01, CpG-containing nucleic acids (wherein cytosine is not methylated), aluminum phosphate, aluminum hydroxide, alum, and combinations thereof. MF59 is 4.3% w / v squalene, 0.5% w / v Tween 80 TM , 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 Adjuvant, MPL, and liposomes. In some cases, the adjuvant comprises QS21 and MPL in a liposomal formulation. In some cases, the adjuvant is AS03. One 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 comprises aluminum hydroxide and MPL. In some cases, the adjuvant is AS04. AS04 comprises aluminum hydroxide and MPL. In some cases, the adjuvant is AS15. AS15 is QS-21 in a liposomal formulation. A combination of an adjuvant, monophosphoryl lipid A, and CpG7909 (an oligonucleotide of the sequence 5'-TCGTCGTTTTGTCGTTTTGTCGTT-3' (SEQ ID NO: 71)). In some cases, the adjuvant is a cyclic dinucleotide (CDN). In some cases, the adjuvant is CpG 1018 (an oligonucleotide of the following sequence: 5'TGACTGTGAACGTTCGAGATGA3' (SEQ ID NO: 72)).

[0087] In some cases, a CDN suitable for use in the immunogenic compositions of the invention is of formula (I):

[0088]

[0089] in:

[0090] A is S or O;

[0091] X is S, N, O, CH2;

[0092] Y, Y' are NH, CH2, O;

[0093] Z, Z' are NH, CH2, O;

[0094] R1 represents hydrogen or NH2 which may be substituted;

[0095] R2 is hydrogen or absent;

[0096] R3 represents NH2, O, OH, H or halogen;

[0097] R4 represents hydrogen, halogen or a linear or branched C1-C6 alkyl group which may be optionally substituted

[0098] R5 represents hydrogen, OH or a linear or branched C1-C6 alkyl chain or a C1-C6 linear or branched alkoxy chain (which may be optionally substituted);

[0099] is a single bond or a double bond;

[0100] Or its conjugate, and salt or solvate thereof. See, for example, US2008 / 0286296.

[0101] In formula (I), in some cases, the purine residue is a guanine (G), adenine (A), a xanthine or hypoxanthine (X) or an inosine (I) residue. The compound may have the same purine residue, such as c-diGMP, c-diAMP, c-diIMP or c-dXMP, or may contain different purine residues, such as c-GpAp, c-GpIp, c-GpXp, c-ApIp, c-ApXp or c-IpXp. In addition, in some cases, R5 is an OH group. In addition, in some cases, X is an oxygen atom. In one embodiment, Y, Y', Z and Z' are oxygen atoms O. Therefore, in one embodiment, the compound of formula (I) is cyclobis(3'-5')diguanylate (c-diGMP) or a conjugate thereof or cyclobis(3'-5')diadenylate (c-diAMP) or a conjugate thereof, or a salt or solvate thereof. In one embodiment, the compound of formula (I) is cyclic bis (3'-5') adenosine monophosphate, also known as c-di-AMP; or a pegylated conjugate. The term "may be substituted" means substitution with a linear or branched C1-C6 alkyl or a linear or branched C1-C6 alkoxy and / or halogen, hydroxyl or carboxyl group.

[0102] In some cases, a CDN suitable for use in an immunogenic composition of the present invention is selected from cyclic diadenosine monophosphate (c-di-AMP), cyclic diguanosine monophosphate (c-di-GMP), and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). In some cases, a CDN suitable for use in an immunogenic composition of the present invention is cGAMP (2'-3'-cyclic GMP-AMP) or cGAMP (3'-3'-cyclic GMP-AMP). In some cases, a CDN suitable for use in an immunogenic composition of the present invention is cGAMP (2'-3'-cyclic GMP-AMP). In some cases, a CDN suitable for use in an immunogenic composition of the present invention is cGAMP (3'-3'-cyclic GMP-AMP).

[0103] In some cases, a CDN suitable for use in the immunogenic compositions of the present invention is of formula (II):

[0104]

[0105] in:

[0106] A, C, A' and C' are independently selected from NH, O and S;

[0107] X, Y, X' and Y' are independently selected from O or S;

[0108] Z and Z' are independently selected from O, S, NH and CH2; and

[0109] B1 and B2 are purines independently selected from the group consisting of:

[0110]

[0111] in:

[0112] Q is hydrogen or NH2;

[0113] The nitrogen is optionally substituted with C1-C6 alkyl or C1-C6 acyl; and

[0114] R is O or S.

[0115] In some cases, a CDN suitable for inclusion in an immunogenic composition of the invention is a fluorinated CDN. In some cases, the fluorinated CDN is 2'-Fc-diGMP having the following structure:

[0116]

[0117] In some cases, the immunogenic composition of the present invention comprises: a) a SLA-SE adjuvant as described above, and a cyclic dinucleotide (CDN); and b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CDN; and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CDN; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CDN; 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.

[0118] In some cases, the immunogenic composition of the present invention comprises: a) a SLA-LSQ adjuvant as described above, and CDN; and b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and CDN; and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and CDN; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and CDN; 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.

[0119] In some cases, the immunogenic composition of the present invention comprises: a) a SLA-SE adjuvant as described above, and 3M-052; and b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and 3M-052; and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and 3M-052; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and 3M-052; 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.

[0120] In some cases, the immunogenic composition of the invention comprises: a) a SLA-LSQ adjuvant as described above, and 3M-052; and b) one or more TPs. The invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and 3M-052; and b) a fusion polypeptide comprising two or more TPs. The invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and 3M-052; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and 3M-052; 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.

[0121] In some cases, the immunogenic composition of the present invention includes: a) a SLA-SE adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and a CpG oligonucleotide (eg, CpG1018); 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.

[0122] In some cases, the immunogenic composition of the invention comprises: a) a SLA-LSQ adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); and b) one or more TPs. The invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); and b) a fusion polypeptide comprising two or more TPs. The invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and a CpG oligonucleotide (e.g., CpG 1018); b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and a CpG oligonucleotide (eg, CpG1018); 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.

[0123] In some cases, the immunogenic composition of the present invention comprises: a) a SLA-SE adjuvant as described above, and AS03; and b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and AS03; and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and AS03; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-SE adjuvant as described above, and AS03; 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.

[0124] In some cases, the immunogenic composition of the present invention comprises: a) a SLA-LSQ adjuvant as described above, and AS03; and b) one or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and AS03; and b) a fusion polypeptide comprising two or more TPs. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and AS03; b) one or more TPs; and c) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer. The present invention provides an immunogenic composition comprising: a) a SLA-LSQ adjuvant as described above, and AS03; 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.

[0125] Compositions containing T cell epitope polypeptides

[0126] As described above, the immunogenic composition of the present invention comprises: a) one or more T cell epitope polypeptides (also referred to herein as "TPs"); or b) a fusion polypeptide comprising two or more TPs.

[0127] Suitable TPs include: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP156 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide.

[0128] Suitable TPs include TP35-NS3 polypeptides, TP50C polypeptides, TP27 polypeptides, TP48 polypeptides, TP65 polypeptides, and TP240 polypeptides as described below. Suitable TPs include TP35-NS3 polypeptides, TP50C polypeptides, TP27 polypeptides, TP48 polypeptides, TP65 polypeptides, TP240 polypeptides, TP156 polypeptides, and TP465 polypeptides as described below.

[0129] In some cases, the TP is from HCV of genotype 1. In some cases, the TP is from HCV of genotype 1a. In some cases, the TP is from HCV of genotype 1b. In some cases, the TP is from HCV of genotype 2. In some cases, the TP is from HCV of genotype 2a. In some cases, the TP is from HCV of genotype 2b. In some cases, the TP is from HCV of genotype 3. In some cases, the TP is from HCV of genotype 3a. In some cases, the TP is from HCV of genotype 4. In some cases, the TP is from HCV of genotype 5. In some cases, the TP is from HCV of genotype 6. In some cases, the TP is from HCV of genotype 7. In some cases, the compositions of the invention comprise TPs of two or more different genotypes of HCV.

[0130] TP35-NS3 peptide

[0131] In some instances, a TP35-NS3 T cell epitope polypeptide ("TP35-NS3 polypeptide") comprises the following amino acid sequence:

[0132] KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), wherein 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; X8 is K or R, wherein 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 cases, the TP35-NS3 polypeptide has a length of 35 amino acids.

[0133] Non-limiting examples of TP35-NS3 polypeptides include:

[0134] 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

[0135] vi) KSTKVPAAYASQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO:75).

[0136] 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 following amino acid sequence:

[0137] KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79), wherein the TP35-NS3 polypeptide is 35 amino acids to 40 amino acids in length (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 is 35 amino acids in length.

[0138] TP50C peptide

[0139] In some instances, a TP50C T cell epitope polypeptide ("TP50C polypeptide") comprises the following amino acid sequence:

[0140] GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X 11 is S, T, H or A; X 12 is A or G; and X 13 It is Q or K, wherein the TP50C T cell epitope polypeptide is 50 amino acids to 60 amino acids in length (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 is 50 amino acids in length.

[0141] In some instances, the TP50-C T cell epitope polypeptide comprises the following amino acid sequence:

[0142] GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X 11 is S, T, H or A; X 12 A or G; X 13 is Q or K; wherein the TP50C T cell epitope polypeptide is 50 amino acids to 60 amino acids in length (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 is 50 amino acids in length.

[0143] Non-limiting examples of TP50C polypeptides include:

[0144] i) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYP (SEQ ID NO: 81);

[0145] ii) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKDRRSTGKSWGKPGYP (SEQ ID NO: 82);

[0146] iii) GVYVLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 83);

[0147] iv) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPTGRSWGQPGYP (SEQ ID NO: 84);

[0148] v) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPTGRHWAQPGYP (SEQ ID NO:85); and

[0149] vi)GVYLLPRRGPRLGVRTTRKSSERSQPRGRRQRIPKAASSQGKAWGKPGYP (SEQ ID NO:86).

[0150] 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 following amino acid sequence:

[0151] GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO: 87), wherein the TP50C T cell epitope polypeptide is 50 amino acids to 60 amino acids in length (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 GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGY P (SEQ ID NO: 87) and is 50 amino acids in length.

[0152] TP23 peptide

[0153] 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"); wherein the TP is 18 amino acids to 23 amino acids in length (e.g., the TP is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids in length). In some cases, the TP is 23 amino acids in length.

[0154] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVX1X2TDALMTGX3TGDFDSVID (SEQ ID NO: 89), wherein X1 is V or C; X2 is A or S; and X3 is F or Y; wherein the length of the TP23 T cell epitope polypeptide is 18 amino acids to 23 amino acids (e.g., the length of TP is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids). In some cases, the length of TP is 23 amino acids.

[0155] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVVATDALMTGYTGDFDSVID (SEQ ID NO: 90); wherein the TP23 polypeptide is 18 to 23 amino acids in length (e.g., TP is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids in length). In some cases, TP is 23 amino acids in length. In some cases, TP is part of a fusion polypeptide, as described in detail below.

[0156] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCATDALMTGFTGDFDSVID (SEQ ID NO: 91); wherein the TP23 T cell epitope polypeptide is 18 to 23 amino acids in length (e.g., the T cell epitope polypeptide is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids in length). In some cases, the TP is 23 amino acids in length. In some cases, the TP is part of a fusion polypeptide, as described in detail below.

[0157] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCSTDALMTGFTGDFDSVID (SEQ ID NO: 92); wherein the TP23 polypeptide is 18 to 23 amino acids in length (e.g., the TP is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids in length). In some cases, the TP is 23 amino acids in length. In some cases, the TP is part of a fusion polypeptide, as described in detail below.

[0158] In some cases, the TP23 polypeptide comprises the following amino acid sequence: DVVVCATDALMTGYTGDFDSVID (SEQ ID NO: 93); wherein the TP23 T cell epitope polypeptide is 18 to 23 amino acids in length (e.g., the T cell epitope polypeptide is 18 amino acids (aa), 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, or 23 amino acids in length). In some cases, the TP23 T cell epitope polypeptide is 23 amino acids in length. In some cases, the TP23 T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0159] 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"); wherein the TP23 polypeptide is 23 amino acids to 30 amino acids in length (e.g., the T cell epitope polypeptide is 23 amino acids (aa), 24 amino acids, 25 amino acids, 26 amino acids, 27 amino acids, 28 amino acids, 29 amino acids, or 30 amino acids in length).

[0160] In some cases, the TP23 polypeptide comprises an amino acid sequence having at least 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 is 23 amino acids in length. In some cases, the TP23 polypeptide comprises the amino acid sequence DVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 88); and is 23 amino acids in length.

[0161] TP27 peptide

[0162] In some cases, the TP27 T cell epitope polypeptide ("TP27 polypeptide") comprises the following 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, wherein 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 cases, the TP27 polypeptide has a length of 27 amino acids.

[0163] Non-limiting examples of TP27 polypeptides include:

[0164] i) LEVIKGGRHLIFCHSKKKCDELAAKLV (SEQ ID NO:95);

[0165] ii)IETIKGGRHLIFCHSKKKCDELAAKLS (SEQ ID NO:96);

[0166] ii)LSYIKGGRHLIFCHSKKKCDELAAALR (SEQ ID NO:97);

[0167] iv) LAFIKGGRHLIFCHSKKKCDELAALR (SEQ ID NO:98);

[0168] v) IAQLKGGRHLIFCHSKKKCDEIASKLR (SEQ ID NO:99);

[0169] vi) LELIKGGRHLIFCHSKKKCDELAQLT (SEQ ID NO: 100);

[0170] vii) LEYIKGGRHLIFCHSKKKCDELAKQLT (SEQ ID NO: 101); viii) LQHIKGGRHLIFCHSKKKCDELAGKLT (SEQ ID NO: 102); and

[0171] ix) LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103).

[0172] 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 following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103), wherein the TP27 polypeptide is 27 amino acids to 32 amino acids in length (e.g., 27, 28, 29, 30, 31, or 32 amino acids). In some cases, the TP27 polypeptide is 27 amino acids in length. In some cases, the TP27 polypeptide comprises the amino acid sequence LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103) and is 27 amino acids in length.

[0173] TP35-NS4 peptide

[0174] In some cases, the TP35-NS4 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:

[0175] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104; also referred to herein as "TP35-NS4"); wherein the T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0176] In some cases, the TP35-NS4 polypeptide comprises 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; wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0177] In some cases, the TP35-NS4 polypeptide comprises 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 10 is V; wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0178] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYV (SEQ ID NO: 106); wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0179] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGQGEGAVQWMNRLIAFASRGNHVAPTHYV (SEQ ID NO: 107); wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0180] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: VLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 108); wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0181] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: ILRRHVGPAEGATQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 109); wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0182] In some cases, the TP35-NS4 polypeptide comprises the following amino acid sequence: IIKRHTGTSEGVTQWMNRLIAFASRGNHVSPTHYI (SEQ ID NO: 110); wherein the TP35-NS4 T cell epitope polypeptide is 28 amino acids to 35 amino acids in length (e.g., the T cell epitope polypeptide is 28 amino acids (aa), 29 amino acids, 30 amino acids, 31 amino acids, 32 amino acids, 33 amino acids, 34 amino acids, or 35 amino acids in length). In some cases, the TP35-NS4 T cell epitope polypeptide is 35 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0183] 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:

[0184] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104); and is 35 amino acids to 40 amino acids in length (e.g., 35 amino acids (aa), 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, or 40 amino acids).

[0185] 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:

[0186] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104); and is 35 amino acids in length. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the invention comprises the amino acid sequence ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYV (SEQ ID NO: 104); and is 35 amino acids in length.

[0187] TP42 peptide

[0188] 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:

[0189] GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 111); and is 33 amino acids to about 50 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, 42 amino acids, or from 42 amino acids to 50 amino acids). 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: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKCKCDELAAKLTG (SEQ ID NO: 111); and is 42 amino acids in length. In some cases, the TP42 polypeptide comprises the amino acid sequence GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKCKCDELAAKLTG (SEQ ID NO: 111); and is 42 amino acids in length.

[0190] In some cases, the TP42 polypeptide comprises 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; X 10 A, K or S; X 11 Is K, Q or A; X 12is T, R or S; and X13 is G or S, wherein n is an integer from 2 to 10, and wherein the TP42 T cell epitope polypeptide has a length of 34 amino acids to 52 amino acids (e.g., 34 amino acids (aa), 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, 42 amino acids, 43 amino acids, 44 amino acids, 45 amino acids, 46 amino acids, 47 amino acids, 48 ​​amino acids, 49 amino acids, 50 amino acids, 51 amino acids, or 52 amino acids). In some cases, the TP42 polypeptide comprises the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX 12 X 13 KKK (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; X 10 A, K or S; X 11 Is K, Q or A; X 12 is T, R, or S; and X 13 is G or S. In some cases, the TP42 polypeptide comprises 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, V or L; X8 is I or L; X9 is L or I; X 10 A, K or S; X 11 Is K, Q or A; X 12 is T, R, V, or S; and X 13is G or S, wherein n is an integer from 2 to 10, and wherein the TP42 T cell epitope polypeptide is 34 amino acids to 52 amino acids in length (e.g., 34 amino acids (aa), 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, 42 amino acids, 43 amino acids, 44 amino acids, 45 amino acids, 46 amino acids, 47 amino acids, 48 ​​amino acids, 49 amino acids, 50 amino acids, 51 amino acids, or 52 amino acids). In some cases, the TP42 polypeptide comprises the following amino acid sequence: X1X2X3GEIPFYGX4AIPX5X6X7X8KGGRHLIFCHSKKKCDEX9AX 10 X 11 LX 12 X 13 KKK (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, V or L; X8 is I or L; X9 is L or I; X 10 A, K or S; X 11 Is K, Q or A; X 12 is T, R, V or S; X 13 is G or S. In some cases, the TP42 T cell epitope polypeptide is 45 amino acids in length. In some cases, the TP42 T cell epitope polypeptide comprises the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTGKKK (SEQ ID NO: 114) and is 45 amino acids in length.

[0191] In some cases, the TP42 polypeptide comprises 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; X 10 A, K or S; X 11 Is K, Q or A; X 12 is T, R, or S; and X 13is G or S; wherein the length of the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the length of the TP42 T cell epitope polypeptide is 42 amino acids. In some cases, the length of the T cell epitope polypeptide is 42 amino acids. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0192] In some cases, the TP42 polypeptide comprises the following amino acid sequence: STTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVA (SEQ ID NO: 115); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0193] In some cases, the TP42 polypeptide comprises the following amino acid sequence: SNTGEIPFYGKAIPIETIKGGRHLIFCHSKKKCDELAAKLSG (SEQ ID NO: 116); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0194] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GQEGEIPFYGRAIPLSYIKGGRHLIFCHSKKKCDELAAALRG (SEQ ID NO: 117); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0195] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GHEGEIPFYGKAIPLAFIKGGRHLIFCHSKKKCDELAALRG (SEQ ID NO: 118); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0196] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GSEGEIPFYGKAIPIAQLKGGRHLIFCHSKKKCDEIASKLRG (SEQ ID NO: 119); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0197] In some cases, a TP42 T cell epitope polypeptide suitable for inclusion in a composition of the invention comprises the following amino acid sequence: PTTGEIPFYGKAIPLELIKGGRHLIFCHSKKKCDELAQLTS (SEQ ID NO: 120); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0198] In some cases, the TP42 polypeptide comprises the following amino acid sequence: PTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAKQLTS (SEQ ID NO: 121); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0199] In some cases, the TP42 polypeptide comprises the following amino acid sequence: PTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAKQLTS (SEQ ID NO: 122); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the TP42 polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0200] In some cases, the TP42 polypeptide comprises the following amino acid sequence: GNDGEIPFYGKAIPLQHIKGGRHLIFCHSKKKCDELAGKLTS (SEQ ID NO: 123); wherein the TP42 T cell epitope polypeptide is 33 amino acids to 42 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, 37 amino acids, 38 amino acids, 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, the TP42 T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is 42 amino acids in length. In some cases, the T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0201] In some cases, a suitable T cell epitope polypeptide is a TP42 polypeptide with 1 to 5 amino acids removed from the N-terminus and / or 1 to 5 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:

[0202] IPFYGKAIPLEQIKGGRHLIFCHSKKKCDELAAKLTG (SEQ ID NO: 124); and is 37 amino acids in length. As another example, a suitable T cell epitope 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 the following amino acid sequence: GTEGEIPFYGKAIPLEQIKGGRHLIFCHSKKKCDELA (SEQ ID NO: 125); and is 37 amino acids in length.

[0203] TP45 peptide

[0204] In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the invention 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 is 45 amino acids to about 50 amino acids in length. In some cases, a T cell epitope polypeptide suitable for inclusion in the compositions of the invention 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 is 45 amino acids in length. In some cases, a T cell epitope polypeptide suitable for inclusion in the compositions of the invention comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNV (SEQ ID NO: 127); and is 45 amino acids in length. In some cases, a T cell epitope polypeptide suitable for inclusion in a composition of the invention comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDKKK (SEQ ID NO: 128); and is 45 amino acids in length.

[0205] In some cases, the TP45 polypeptide comprises the following amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 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; X 10 A or S; X 11is F or Y; X 12 is C or K; X 13 is N or K; and X 14 is V or K, wherein n is an integer from 2 to 10, and wherein the length of the TP45 T cell epitope polypeptide is from 36 amino acids to 55 amino acids. In some cases, the TP45 polypeptide comprises the following amino acid sequence:

[0206] X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX11TGDFDSV IDX 12 X 13 X 14 KKK (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; X 10 A or S; X 11 is F or Y; X 12 is C or K; X 13 is N or K; and X 14 is V or K; wherein the TP45 T cell epitope polypeptide is 48 amino acids in length. In some cases, the TP45 T cell epitope polypeptide comprises the following amino acid sequence: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCNVKKK (SEQ ID NO: 131) and is 48 amino acids in length.

[0207] In some cases, the TP45 polypeptide comprises 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; X 10 A or S; X 11 is F or Y; X 12 is C or K; X 13 is N or K; and X 14is V or K; and wherein the length of the TP45 T cell epitope polypeptide is 36 amino acids to 55 amino acids. In some cases, the length of the TP45 T cell epitope polypeptide is 45 amino acids. In some cases, the TP45 T cell epitope polypeptide is part of a fusion polypeptide, as described in detail below.

[0208] In some cases, the TP45 polypeptide comprises 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; X 10 Yes A; X 11 is F or Y; X 12 It is K; X 13 It is K; X 14 is K; and wherein the TP45 T cell epitope polypeptide is 36 amino acids to 55 amino acids in length. In some cases, the TP45 T cell epitope polypeptide is 45 amino acids in length.

[0209] In some cases, a suitable T cell epitope polypeptide is a TP45 polypeptide with 1 to 5 amino acids removed from the N-terminus and / or 1 to 5 amino acids removed from the C-terminus. Thus, for example, in some cases, the 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 polypeptide: LNAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 133); and a length of 43 amino acids. For example, in some cases, the TP45 polypeptide comprises the amino acid sequence LNAVAYYRGLDVSVIPTSGDVVVVVATDALMTGFTGDFDSVID (SEQ ID NO: 133); and is 43 amino acids in length.

[0210] T48 peptide

[0211] In some instances, a TP48 T cell epitope polypeptide ("TP48 polypeptide") comprises the following amino acid sequence:

[0212] X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19 L (SEQ ID NO: 134), 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; 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 A, Q, R or K; X 16 is R, K or X; X 17 is T or M; X 18 is Q, A or T or G; and X 19 It is I, L or V, wherein 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.

[0213] Non-limiting examples of TP48 polypeptides include:

[0214] i) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAIL (SEQ ID NO: 135);

[0215] ii) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136);

[0216] iii) ILRRHVGPGEGAVQWMNRLIAFASRGNHVAPTHYVTESDASQRVTQLL (SEQ ID NO: 137);

[0217] iv) ILRRHVGQGEGAVQWMNRLIAFASRGNHVAPTHYVAESDASQRVTQVL (SEQ ID NO: 138);

[0218] v) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTALL (SEQ ID NO: 139);

[0219] vi) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136);

[0220] vii) VLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYVPETDASAKVTQLL (SEQ ID NO: 140);

[0221] viii) IIKRHTGTSEGVTQWMNRLIAFASRGNHVSPTHYIQDDDSKRVMGIL (SEQ ID NO: 141);

[0222] ix) ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136).

[0223] 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 following amino acid sequence:

[0224] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), wherein the TP48 T cell epitope polypeptide is 48 amino acids to 53 amino acids in length (e.g., 48, 49, 50, 51, 52, or 53 amino acids). In some cases, the TP48 polypeptide is 48 amino acids in length. In some cases, the TP48 polypeptide comprises the amino acid sequence:

[0225] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), and is 48 amino acids in length.

[0226] TP33 peptide

[0227] 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 is 33 amino acids to about 37 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, or 37 amino acids in length), or is 30 amino acids to about 33 amino acids in length (e.g., 30 amino acids (aa), 31 amino acids, 32 amino acids, or 33 amino acids in length). 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 is 33 amino acids in length. In some cases, the TP33 polypeptide comprises the amino acid sequence HSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 142); and is 33 amino acids in length.

[0228] In some cases, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), wherein 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; X7 is V or I; and is 33 amino acids to about 37 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, or 37 amino acids in length), or is 30 amino acids to about 33 amino acids in length (e.g., 30 amino acids (aa), 31 amino acids, 32 amino acids, or 33 amino acids in length). In some cases, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), wherein 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; X7 is V or I; wherein the TP33 T cell epitope polypeptide has a length of 33 amino acids.

[0229] In some cases, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 144), wherein X1 is V, S, R, or T; X2 is A or G; X3 is L or M; X4 is I, L, or V; and is 33 amino acids to about 37 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, or 37 amino acids in length), or is 30 amino acids to about 33 amino acids in length (e.g., 30 amino acids (aa), 31 amino acids, 32 amino acids, or 33 amino acids in length). In some cases, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 144), wherein X1 is V, S, R or T; X2 is A or G; X3 is L or M; X4 is I, L or V; wherein the TP33 T cell epitope polypeptide is 33 amino acids in length.

[0230] In some cases, the TP33 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 is 33 amino acids to about 37 amino acids in length (e.g., 33 amino acids (aa), 34 amino acids, 35 amino acids, 36 amino acids, or 37 amino acids in length), or is 30 amino acids to about 33 amino acids in length (e.g., 30 amino acids (aa), 31 amino acids, 32 amino acids, or 33 amino acids in length). In some cases, the TP33 polypeptide comprises the following amino acid sequence: HSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 145), wherein X1 is I, L, or V; and X2 is V or I; wherein the TP33 T cell epitope polypeptide is 33 amino acids in length.

[0231] In some cases, the TP33 polypeptide comprises the amino acid sequence HSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIP (SEQ ID NO: 146); and is 33 amino acids in length.

[0232] TP42-2 polypeptide

[0233] In some cases, 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 a length of 42 amino acids to about 46 amino acids (e.g., a length of 42 amino acids (aa), 43 amino acids, 44 amino acids, 45 amino acids, or 46 amino acids), or a length of 38 amino acids to about 42 amino acids (e.g., a length of 38 amino acids (aa), 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids). In some cases, 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 is 42 amino acids in length. In some cases, the T42-2 polypeptide comprises the amino acid sequence KGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIP (SEQ ID NO: 147); and is 42 amino acids in length.

[0234] In some cases, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), wherein 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 is 42 amino acids to about 46 amino acids in length (e.g., 42 amino acids (aa), 43 amino acids, 44 amino acids, 45 amino acids, or 46 amino acids in length), or is 38 amino acids to about 42 amino acids in length (e.g., 38 amino acids (aa), 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids in length). In some cases, the T42-2 polypeptide comprises the following amino acid sequence:

[0235] KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), wherein 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; wherein the T42-2 polypeptide has a length of 42 amino acids.

[0236] In some cases, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 149), wherein 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 is 42 amino acids to about 46 amino acids in length (e.g., 42 amino acids (aa), 43 amino acids, 44 amino acids, 45 amino acids, or 46 amino acids in length), or is 38 amino acids to about 42 amino acids in length (e.g., 38 amino acids (aa), 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids in length). In some cases, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAKLX1X2X3GX4NAVAYYRGLDVSVIP (SEQ ID NO: 149), wherein X1 is V, S, R or T; X2 is A or G; X3 is L or M; X4 is I, L or V; wherein the T42-2 polypeptide is 42 amino acids in length.

[0237] In some cases, the T42-2 polypeptide comprises the following amino acid sequence: KGGRHLIFCHSKKKCDELAAALRGMGX1NAVAYYRGLDVSX1IP (SEQ ID NO: 150), wherein X1 is I, L, or V; and X2 is V or I; and is 42 amino acids to about 46 amino acids in length (e.g., 42 amino acids (aa), 43 amino acids, 44 amino acids, 45 amino acids, or 46 amino acids in length), or is 38 amino acids to about 42 amino acids in length (e.g., 38 amino acids (aa), 39 amino acids, 40 amino acids, 41 amino acids, or 42 amino acids in length). In some cases, 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; wherein the T42-2 polypeptide is 42 amino acids in length.

[0238] In some cases, the T42-2 polypeptide comprises the amino acid sequence KGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIP (SEQ ID NO: 151); and is 42 amino acids in length.

[0239] TP65 peptide

[0240] In some cases, the 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 is 65 amino acids to 70 amino acids in length (e.g., 65, 66, 67, 68, 69, or 70 amino acids). In some cases, the 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 is 65 amino acids in length. In some cases, the TP is 65 amino acids in length. In some cases, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGSSYGFQYS (SEQ ID NO: 153), and is 65 amino acids in length. In some cases, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPTKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGASYGFQYS (SEQ ID NO: 154), and is 65 amino acids in length. In some cases, the TP65 polypeptide has the following amino acid sequence: TPIDTTIMAKNEVFCVDPVKGGRKPARLIVYPDLGVRVCEKMALYDVVQKLPQAVMGPSYGFQYS (SEQ ID NO: 155).

[0241] TP240 peptide

[0242] In some cases, the TP240 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:

[0243] SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKA HGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSX1DA TTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGX2EGEIPFY GKAIPLX3X4IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVI PTX5GDVVVVATDALMTGYTGDFDSVIDCNVAVTQT(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; and the length is 240 amino acids to 245 amino acids (e.g., 240, 241, 242, 243, 244 or 245 amino acids). In some cases, the length of TP is 240 amino acids.

[0244] In some cases, the TP240 polypeptide has the following amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 157), and is 240 amino acids in length. In some cases, the TP240 polypeptide has the following amino acid sequence: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSVDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGNEGEIPFYGKAIPLSTIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTQGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 158), and is 240 amino acids in length.

[0245] TP465 peptide

[0246] In some cases, the TP465 polypeptide comprises Figures 11A-11C Any of the TP465 polypeptide amino acid sequences shown has an amino acid sequence with 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 a length of 460 amino acids to 470 amino acids, for example, a length of 465 amino acids.

[0247] In some cases, 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 the following amino acid sequence:

[0248] SFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAET AGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCN TCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHF LSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPVTKYIMTCMSADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRI(SEQ ID NO:159); and is 465 amino acids in length.

[0249] TP156 peptide

[0250] In some cases, the TP156 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:

[0251] KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160); and is about 150 amino acids to about 169 amino acids in length; for example, is 156 amino acids in length.

[0252] TP29 peptide

[0253] In some cases, the TP29 polypeptide comprises Fig.12 The TP29 amino acid sequence shown has an amino acid sequence with 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 is about 29 amino acids in length. 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 wherein the TP29 polypeptide is 29 amino acids in length.

[0254] TP50-NS2 peptide

[0255] In some cases, the TP50-NS2 polypeptide comprises Fig.12The TP50-NS2 amino acid sequences shown have an amino acid sequence with 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 are about 50 amino acids in length. 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 wherein the TP50-NS2 polypeptide is 50 amino acids in length.

[0256] TP52 peptide

[0257] In some cases, the TP52 polypeptide comprises Fig.12 The TP52 amino acid sequence shown has an amino acid sequence of 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 is 52 amino acids in length. For example, in one instance, the TP52 polypeptide comprises the following amino acid sequence: AIPLX(EA)X(VTYFL)IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYY RGLDVSVIPT X(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 wherein the TP52 polypeptide is 52 amino acids in length.

[0258] TP70 peptide

[0259] In some cases, the TP70 polypeptide comprises Fig.12The TP70 amino acid sequences shown have an amino acid sequence with 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 are about 70 amino acids in length. For example, in some cases, the TP70 polypeptide comprises Fig.12 The TP70 amino acid sequence shown, wherein X is Ser or Gln; and wherein the TP70 polypeptide is 70 amino acids in length.

[0260] TP100 peptide

[0261] In some cases, the TP100 polypeptide comprises Fig.12 The TP100 amino acid sequences shown have an amino acid sequence with 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 are about 100 amino acids in length. For example, in some cases, the TP100 polypeptide comprises Fig.12 The TP100 amino acid sequence shown, wherein the first "X" is Thr, Asn, Gln, His or Ser, wherein the second "X" is Glu or Ala, the third "X" is Val, Thr, Tyr, Phe or Leu, and the fourth "X" is Ser or Gln; and wherein the TP100 polypeptide has a length of 100 amino acids.

[0262] TP171 peptide

[0263] In some cases, TP171 comprises Fig.12 The TP171 amino acid sequence shown has an amino acid sequence of 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 is about 171 amino acids in length.

[0264] TP228 peptide

[0265] In some cases, TP228 contains Fig.12The TP228 amino acid sequence shown has an amino acid sequence of 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 is about 228 amino acids in length.

[0266] The TP228 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 the following TP228 amino acid sequence:

[0267] LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSX1DATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGX2EGEIPFYGKAIPLX3X4IKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTX5GDVVVVATDALMTGYTGDFDSVIDCN (SEQ ID NO: 161), wherein X1 is Thr or Val; X2 is Thr, Asn, Gln, His or Ser; X3 is Glu or Ala; X4 is Val, Thr, Tyr, Phe or Leu; and X5 is Ser or Gln; and the length can be 228 amino acids.

[0268] For example, a TP228 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 the following amino acid sequence:

[0269] LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARL VVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCN(SEQ ID NO:162); and can be 215 amino acids (aa) to 235 amino acids in length (e.g., 215 amino acids, 216 amino acids, 217 amino acids, 218 amino acids, 219 amino acids, 220 amino acids, 221 amino acids, 222 amino acids, 223 amino acids, 224 amino acids, 225 amino acids, 226 amino acids, 227 amino acids, 228 amino acids, 229 amino acids, 230 amino acids, 231 amino acids, 232 amino acids, 233 amino acids, 234 amino acids, or 235 amino acids). In some cases, the TP228 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:

[0270] LHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSILGIGTVLDQAETAGARL VVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGFTGDFDSVIDCN(SEQ ID NO:163); and is 228 amino acids in length.

[0271] TP553 peptide

[0272] In some cases, the TP553 polypeptide comprises Fig.12The TP553 amino acid sequence shown has an amino acid sequence of 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 is about 553 amino acids in length.

[0273] TP778 peptide

[0274] In some cases, the TP778 polypeptide comprises Fig.12 The TP778 amino acid sequence shown in has an amino acid sequence of 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 is about 778 amino acids in length.

[0275] TP1987 peptide

[0276] In some cases, the TP1987 polypeptide comprises Fig.12 The TP1987 amino acid sequence shown has an amino acid sequence with 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 is about 1987 amino acids in length.

[0277] Compositions containing a single TP

[0278] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is 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 TP15 6 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is 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; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimers; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0279] In some cases, the immunogenic composition of the invention comprises: a) a single TP, wherein the TP is 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) a SLA formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) a single TP, wherein the TP is 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) a SLA formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0280] In some cases, the immunogenic composition of the invention comprises: a) a single TP, wherein the TP is 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) a SLA formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) a single TP, wherein the TP is 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) a SLA formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0281] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP35-NS3 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP35-NS3 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0282] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP27 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP27 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0283] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP48 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP48 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0284] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP50C polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP50C polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0285] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP65 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP65 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0286] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP240 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP240 polypeptide; 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 comprising a saponin.

[0287] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP156 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP156 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0288] In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP465 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) a single TP, wherein the TP is a TP465 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0289] Compositions containing two TPs

[0290] In some cases, the immunogenic composition of the invention comprises: a) only two TPs, wherein the two TPs are selected from the following: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP1 56 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic compositions of the invention comprise: a) only two TPs, wherein the two TPs are selected from the following: 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; viiii) 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; 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 a saponin.

[0291] In some cases, the immunogenic composition of the invention comprises: a) only two TPs, wherein the two TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) only two TPs, wherein the two TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0292] In some cases, the immunogenic composition of the invention comprises only: a) two TPs, wherein the two TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) only two TPs, wherein the two TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0293] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP35-NS3 polypeptide and a TP27 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are 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) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0294] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP27 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP27 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0295] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP27 polypeptide and a TP50C polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP27 polypeptide and a TP50C polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0296] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP35-NS3 polypeptide and a TP48 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are 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) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0297] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP35-NS3 polypeptide and TP50C polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP35-NS3 polypeptide and TP50C polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0298] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP50C polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP50C polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0299] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP156 polypeptide and TP465 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP156 polypeptide and TP465 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0300] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP156 polypeptide and TP48 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP156 polypeptide and TP48 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0301] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP48 polypeptide and TP465 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP48 polypeptide and TP465 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0302] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP65 polypeptide; and b) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are a TP48 polypeptide and a TP65 polypeptide; b) an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer; and c) a SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0303] In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP465 polypeptide and TP65 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) two TPs, wherein the two TPs are TP465 polypeptide and TP65 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0304] Composition containing three TPs

[0305] In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP1 56 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP156 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0306] In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0307] In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) only three TPs, wherein the three TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0308] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP35-NS3 polypeptide, TP48 polypeptide, and TP27 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP35-NS3 polypeptide, TP48 polypeptide, and TP27 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0309] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP48 polypeptide, and TP27 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP48 polypeptide, and TP27 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0310] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP48 polypeptide, and TP35-NS3 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP48 polypeptide, and TP35-NS3 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0311] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP27 polypeptide, and TP35-NS3 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP50C polypeptide, TP27 polypeptide, and TP35-NS3 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0312] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP465 polypeptide and TP48 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP465 polypeptide and TP48 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0313] In some cases, the immunogenic composition of the present invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP465 polypeptide and TP65 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the present invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP465 polypeptide and TP65 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0314] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP465 polypeptide, TP48 polypeptide and TP65 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP465 polypeptide, TP48 polypeptide and TP65 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0315] In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP48 polypeptide and TP65 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) three TPs, wherein the three TPs are TP156 polypeptide, TP48 polypeptide and TP65 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0316] Composition containing four TPs

[0317] In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP1 56 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin. In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: i) TP35-NS3 polypeptide; ii) TP50C polypeptide; iii) TP23 polypeptide; iv) TP27 polypeptide; v) TP35-NS4 polypeptide; vi) TP42 polypeptide; vii) TP45 polypeptide; viii) TP48 polypeptide; ix) TP33 polypeptide; x) TP42-2 polypeptide; xi) TP65 polypeptide; xii) TP240 polypeptide; xiii) TP156 polypeptide; xiv) TP465 polypeptide; xv) TP29 polypeptide; xvi) TP50-NS2 polypeptide; xvii) TP52 polypeptide; xviii) TP70 polypeptide; xix) TP100 polypeptide; xx) TP171 polypeptide; xxi) TP228 polypeptide; xxii) TP553 polypeptide; xxiii) TP778 polypeptide; and xxiv) TP1987 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising a saponin.

[0318] In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide and TP240 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0319] In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; and b) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) only four TPs, wherein the four TPs are selected from the following: TP35-NS3 polypeptide, TP50C polypeptide, TP27 polypeptide, TP48 polypeptide, TP65 polypeptide, TP240 polypeptide, TP156 polypeptide and TP465 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in the following: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0320] In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP35-NS3 polypeptide, TP48 polypeptide, TP50C polypeptide, and TP27 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP35-NS3 polypeptide, TP48 polypeptide, TP50C polypeptide, and TP27 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0321] In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP240 polypeptide, TP48 polypeptide, TP65 polypeptide and TP50C polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP240 polypeptide, TP48 polypeptide, TP65 polypeptide and TP50C polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0322] In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP156 polypeptide, TP465 polypeptide, TP48 polypeptide, and TP65 polypeptide; and b) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin. In some cases, the immunogenic composition of the invention comprises: a) four TPs, wherein the four TPs are TP156 polypeptide, TP465 polypeptide, TP48 polypeptide, and TP65 polypeptide; b) HCV E1 polypeptide, HCV E2 polypeptide, or HCV E1 / E2 heterodimer; and c) SLA, formulated in: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0323] Compositions containing T cell epitope fusion polypeptides

[0324] As described above, in some cases, the immunogenic composition of the present invention comprises a T cell epitope fusion polypeptide, ie, a fusion polypeptide comprising two or more of the aforementioned T cell epitope polypeptides. T cell epitope fusion polypeptides are also referred to herein as "TP fusion polypeptides".

[0325] In some cases, the TP fusion polypeptide does not include a connecting peptide between any two TP polypeptides. In some cases, the TP fusion polypeptide comprises a connecting peptide between any two TP polypeptides. If the TP fusion polypeptide comprises one or more connecting peptides, the one or more connecting peptides are independently 1 to 10 amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids) in length. If the TP fusion polypeptide comprises one or more connecting peptides, the one or more connecting peptides are independently selected from: for example, (GGGGS)n (SEQ ID NO: 163), wherein 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), wherein n is an integer between 1 and 5 (e.g., n is 1, 2, 3, 4 or 5).

[0326] 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 include any other polypeptides.

[0327] 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 include any other polypeptides.

[0328] 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 aforementioned TP polypeptides and does not include any other polypeptide. In some cases, the total length of the TP fusion polypeptide is 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 total length of the TP fusion polypeptide is 160 amino acids.

[0329] 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: i) a TP35-NS3 polypeptide; ii) a TP27 polypeptide; iii) a TP48 polypeptide; and iv) a TP50C polypeptide. 2) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) a TP35-NS3 polypeptide; ii) a TP27 polypeptide; iii) a TP50C polypeptide; and iv) a TP48 polypeptide. 3) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) a TP35-NS3 polypeptide; ii) a TP48 polypeptide; iii) a TP27 polypeptide; and iv) a TP50C polypeptide. 4) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: 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: 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: 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: 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, the TP fusion polypeptide comprises, from N-terminus to C-terminus: 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: 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: 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: 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: i) TP27 polypeptide; ii) TP50C polypeptide; iii) TP35-NS3 polypeptide; and iv) TP48 polypeptide. 13) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP27 polypeptide; iii) TP35-NS3 polypeptide; and iv) TP50C polypeptide. 14) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP27 polypeptide; iii) TP50C polypeptide; and iv) TP35-NS3 polypeptide. 15) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP35-NS3 polypeptide; iii) TP27 polypeptide; and iv) TP50C polypeptide. 16) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP35-NS3 polypeptide; iii) TP50C polypeptide; and iv) TP27 polypeptide. 17) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP50C polypeptide; iii) TP27 polypeptide; and iv) TP35-NS3 polypeptide. 18) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP48 polypeptide; ii) TP50C polypeptide; iii) TP35-NS3 polypeptide; and iv) TP27 polypeptide. 19) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP50C polypeptide; ii) TP27 polypeptide; iii) TP35-NS3 polypeptide; and iv) TP48 polypeptide. 20) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP50C polypeptide; ii) TP27 polypeptide; iii) TP48 polypeptide; and iv) TP35-NS3 polypeptide. 21) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP50C polypeptide; ii) TP35-NS3 polypeptide; iii) TP27 polypeptide; and iv) TP48 polypeptide. 22) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP50C polypeptide; ii) TP35-NS3 polypeptide; iii) TP48 polypeptide; and iv) TP27 polypeptide. 23) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP50C polypeptide; ii) TP48 polypeptide; iii) TP27 polypeptide; and iv) TP35-NS3 polypeptide.24) As another example, in some cases, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) a TP50C polypeptide; ii) a TP48 polypeptide; iii) a TP35-NS3 polypeptide; and iv) a TP27 polypeptide.

[0330] As a non-limiting example, the TP fusion polypeptide comprises, from N-terminus to C-terminus: i) TP35-NS3 polypeptide; ii) TP27 polypeptide; iii) TP48 polypeptide; and iv) TP50C polypeptide. In some cases, the TP fusion 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 with the following amino acid sequence:

[0331] KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKLEQIKGGRHLIFCHSK

[0332] KKCDELAAKLRILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESD

[0333] AAARVTQILGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP(SEQ IDNO:172),

[0334] wherein: i) KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO:79) is a TP35-NS3 polypeptide, ii) LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO:103) is a TP27 polypeptide; iii) ILRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO:136) is a TP48 polypeptide, and iv) GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP (SEQ ID NO:87) is a TP50C polypeptide. In some cases, the total length of the TP fusion polypeptide is 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 total length of the TP fusion polypeptide is 160 amino acids.

[0335] In some cases, the TP fusion polypeptide comprises a TP240 polypeptide, a TP48 polypeptide, a TP65 polypeptide, and a TP50C polypeptide, and does not include any other polypeptides. The total length of the TP fusion polypeptide can be 410 amino acids to 415 amino acids (e.g., 410, 411, 412, 413, 414, or 415 amino acids). In some cases, the length of the TP fusion polypeptide is 410 amino acids. The four TP polypeptides can 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: i) TP240 polypeptide; ii) TP48 polypeptide; and iii) TP65 polypeptide; iv) TP50C polypeptide. As an example, the TP fusion polypeptide may comprise Fig.10 The amino acid sequences shown have an amino acid sequence with at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% amino acid sequence identity, 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; wherein the length of the TP fusion polypeptide is 410 amino acids to 415 amino acids (e.g., 410, 411, 412, 413, 414 or 415 amino acids).

[0336] HCVE1 polypeptide, HCVE2 polypeptide and HCVE1 / E2 heterodimer

[0337] As described above, in some cases, the immunogenic compositions of the invention comprise an HCV E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimer.

[0338] E1 polypeptide

[0339] HCV E1 polypeptides suitable for inclusion in the immunogenic compositions of the present invention or in the HCV E1 / E2 heterodimers present in the immunogenic compositions of the present invention can be from about 100 amino acids (aa) to about 150 amino acids, from about 150 amino acids to about 175 amino acids, from about 175 amino acids to about 195 amino acids, from about 131 amino acids to about 175 amino acids, or from about 175 amino acids to about 193 amino acids in length. In some cases, the HCV E1 polypeptide is an HCV E1 extracellular domain polypeptide. In some cases, the HCV E1 polypeptide is a full-length HCV E1 polypeptide.

[0340] exist Figures 1A-1C In the present invention, the amino acid sequence of E1 is amino acid 192 to amino acid 383. Figure 2A-2C In the present invention, the amino acid sequence of E1 is amino acid 192 to amino acid 383. Figures 3A-3CIn the present invention, the amino acid sequence of E1 is amino acid 192 to amino acid 384. Figure 4A-4B In, the amino acid sequence of E1 is 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 a precursor E1 protein (including a signal sequence); includes a mature E1 polypeptide lacking the sequence; and includes an E1 polypeptide with a heterologous signal sequence. The E1 polypeptide may include a C-terminal membrane anchoring sequence present at about amino acid positions 360-383 (see, e.g., WO 96 / 04301). In some cases, a suitable E1 polypeptide lacks a C-terminal portion including a transmembrane region. For example, in some cases, a suitable E1 polypeptide lacks a C-terminal portion from amino acid 330 to amino acid 384 or from amino acid 360 to amino acid 384. The E1 polypeptide may be an E1 polypeptide of any genotype, subtype, or isolate of HCV. E1 polypeptides of genotype 1 and E1 polypeptides of genotype 3 are included in the E1 / E2 heterodimer of the present invention.

[0341] The E1 polypeptide may comprise Figures 1A-1C , Figure 2A-2C , Figures 3A-3C or Figure 4A-4B The amino acid sequences of the El polypeptides shown have an amino acid sequence of 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.

[0342] The E1 polypeptide may comprise Figures 1A-1C The amino acid sequence of the E1 polypeptide shown has 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. For example, an E1 polypeptide of genotype 1A can comprise an amino acid sequence that is identical to the E1 polypeptide identified as 1A and shown in Figures 1A-1C 1B has 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 of. For example, an E1 polypeptide of genotype 1B can comprise an amino acid sequence that is identical to amino acids 192-383 of the amino acid sequence labeled 1B and shown in Figures 1A-1C amino acid sequences 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. For example, an E1 polypeptide of genotype 1C 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 192-383 of the amino acid sequence labeled 1C and shown in 1A-1C.

[0343] The E1 polypeptide may comprise Figure 2A-2C The amino acid sequence of the E1 polypeptide shown has 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. For example, an E1 polypeptide of genotype 2A can comprise an amino acid sequence that is identical to the E1 polypeptide labeled 2A and shown in Figure 2A-2C 192-383 of the amino acid sequence of genotype 2B 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. For example, an E1 polypeptide of genotype 2B can comprise an amino acid sequence that is identical to amino acids 192-383 of the amino acid sequence labeled 2B and shown in Figure 2A-2C amino acid sequences 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.

[0344] The E1 polypeptide may comprise Figures 3A-3CThe consensus E1 polypeptide amino acid sequences shown have amino acid sequences 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.

[0345] The E1 polypeptide may comprise Figure 4A-4B The amino acid sequence of the E1 polypeptide shown has 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. For example, the 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. Figure 4A-4B Amino acids 192-383 of the shown amino acid sequence have an amino acid sequence with 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.

[0346] E2 polypeptide

[0347] The E2 polypeptide suitable for inclusion in the immunogenic composition of the present invention or included in the HCV E1 / E2 heterodimer present in the immunogenic composition of the present invention can be about 200 amino acids (aa) to about 250 amino acids, about 250 amino acids to about 275 amino acids, about 275 amino acids to about 300 amino acids, about 300 amino acids to about 325 amino acids, about 325 amino acids to about 350 amino acids, or about 350 amino acids to about 365 amino acids in length. In some cases, the HCV E2 polypeptide is an HCV E2 extracellular domain polypeptide. In some cases, the HCV E2 polypeptide is a full-length HCV E2 polypeptide.

[0348] exist Figure 1A -AC, the amino acid sequence of E2 is from amino acid 384 to amino acid 746. Figure 2A-2B In the present invention, the amino acid sequence of E2 is amino acid 384 to amino acid 751. Figures 3A-3C In the present invention, the amino acid sequence of E2 is amino acid 385 to amino acid 754. Figure 4A-4BIn the present invention, the amino acid sequence of E2 is amino acid 384 to amino acid 750. As used herein, "E2 polypeptide" includes precursor E2 protein (including signal sequence); includes mature E2 polypeptide lacking such sequence; and includes E2 polypeptide with heterologous signal sequence. E2 polypeptide can include C-terminal membrane anchor sequence, which is present at about amino acid position 715-730 and can extend to about amino acid residue 746 (see Lin et al., J. Virol. (1994) 68: 5063-5073).

[0349] In some cases, 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, wherein the amino acids are numbered with reference to Figures 1A-1C See, e.g., U.S. Pat. No. 6,521,423.

[0350] E2 polypeptides suitable for inclusion in the immunogenic compositions of the present invention may include Figures 1A-1C , Figure 2A-2C , Figures 3A-3C or Figure 4A-4B The amino acid sequence of the E2 polypeptide shown has 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. E2 polypeptides suitable for inclusion in the immunogenic compositions of the invention may include amino acid sequences with Figures 1A-1C , Figure 2A-2C , Figures 3A-3C or Figure 4A-4B The amino acid sequences of the E2 polypeptides shown have amino acid sequences with 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.

[0351] The E2 polypeptide may comprise Figures 1A-1C The amino acid sequence of the E2 polypeptide shown has 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. For example, the E2 polypeptide of genotype 1 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. Figures 1A-1CThe amino acid sequences of the polypeptides of the invention may have 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 shown. For example, an E2 polypeptide of genotype 1A may comprise an amino acid sequence that is identical to amino acids 1A and shown in Figures 1A-1C , 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 of . For example, an E2 polypeptide of genotype 1B can comprise an amino acid sequence that is identical to amino acids 384-746 of the amino acid sequence labeled 1B and shown in Figures 1A-1C 84-746 of the amino acid sequence of genotype 1C. For example, the E2 polypeptide of genotype 1C can comprise an amino acid sequence that is 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 of genotype 1C. Figures 1A-1C amino acid sequences 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.

[0352] The E2 polypeptide may comprise Figure 2A-2C The amino acid sequence of the E2 polypeptide shown has 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. For example, the 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. Figure 2A-2CAn 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 shown. For example, an E2 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 384-751 of the amino acid sequence shown. Figure 2A-2C 384-751 of the "consensus" amino acid sequence shown have 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. For example, the E2 polypeptide of genotype 2B may comprise an amino acid sequence that is identical to Figure 2A-2C Amino acids 384-751 of the "consensus" amino acid sequence shown have an amino acid sequence with 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.

[0353] The E2 polypeptide may comprise Figures 3A-3C The amino acid sequence of the E2 polypeptide shown has 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. For example, the E2 polypeptide of genotype 3 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. Figures 3A-3C The amino acid sequences of the polypeptides of the invention may have 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 shown. For example, an E2 polypeptide of genotype 3A may comprise an amino acid sequence that is identical to amino acids 385-754 of the amino acid sequence identified as 3A and shown in Figures 3A-3C, 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 of . For example, an E2 polypeptide of genotype 3B can comprise an amino acid sequence that is identical to amino acids 385-754 of the amino acid sequence labeled 3B and shown in Figures 3A-3C , 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 of . For example, an E2 polypeptide of genotype 3K can comprise an amino acid sequence that is identical to amino acids 385-754 of the amino acid sequence identified as 3K and shown in Figures 3A-3C amino acid sequences 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.

[0354] The E2 polypeptide may comprise Figure 4A-4B The amino acid sequence of the E2 polypeptide shown has 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. For example, the 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. Figure 4A-4B Amino acids 384-750 of the shown amino acid sequence have an amino acid sequence of 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.

[0355] HCV E1 / E2 heterodimer

[0356] HCV E1 / E2 heterodimers suitable for use in the immunogenic compositions of the present invention include: HCV E1 / E2 heterodimers comprising wild-type HCV E1 polypeptides; HCV E1 / E2 heterodimers comprising wild-type HCV E2 polypeptides; HCV E1 / E2 heterodimers comprising variant HCV E1 polypeptides; and HCV E1 / E2 heterodimers comprising variant HCV E2 polypeptides. HCV E2 polypeptides suitable for use in the immunogenic compositions of the present invention include wild-type E2 polypeptides and variant E2 polypeptides. HCV E1 polypeptides suitable for use in the immunogenic compositions of the present invention include wild-type E1 polypeptides and variant E1 polypeptides. HCV E1 / E2 heterodimers may include any of the aforementioned HCV E1 polypeptides and any of the aforementioned HCV E2 polypeptides.

[0357] container

[0358] The invention provides a container comprising an immunogenic composition of the invention. 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.

[0359] Methods of inducing an immune response

[0360] The present invention provides a method of inducing an immune response (eg, a protective immune response) against at least one HCV genotype in a mammalian subject, wherein the method comprises administering to the individual an effective amount of an immunogenic composition of the present invention.

[0361] In some cases, a prime-boost vaccine regimen is used. In some cases, a first (prime-boost) immunogenic composition is administered, and after a period of time, a second (boost) immunogenic composition is administered. In some cases, the first immunogenic composition and the second immunogenic composition are identical. In some cases, the first immunogenic composition and the second immunogenic composition are different. For example, in some cases, the first immunogenic composition comprises a first TP fusion polypeptide; the second immunogenic composition comprises a second TP fusion polypeptide, and the second TP fusion polypeptide has an amino acid sequence different from the first TP fusion polypeptide. The second immunogenic composition can be administered in a time period of 1 day to 1 year after the first immunogenic composition is administered. For example, the second immunogenic composition can be administered in a time period of 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 the first immunogenic composition is administered.

[0362] General Considerations

[0363] The immunogenic compositions of the present invention are typically administered to human subjects who: i) suffer from HCV infection; or ii) are at risk of acquiring HCV infection (e.g., at a higher risk of acquiring HCV infection than the general population); or iii) are infected with HCV for the first time, to prevent or at least partially halt the development of the disease and its complications. An amount sufficient to achieve this goal is defined as a "therapeutically effective dose" or "therapeutically effective amount". The "preventive" use of the immunogenic composition generally refers to administration to individuals who are not infected with HCV (e.g., "prime immunized" individuals). The "therapeutic" use of the immunogenic composition may refer to "preventive" use (administered to individuals who are not infected with HCV) and / or administration to individuals who suffer from HCV infection. The "therapeutically effective amount" of the immunogenic composition of the present invention may be an amount that effectively induces an individual's immune response to HCV when administered to an individual who is not infected with HCV in one or more doses. The "therapeutically effective amount" of the immunogenic composition of the present invention may be an amount that effectively enhances an individual's immune response to HCV when administered to an individual infected with HCV in one or more doses.

[0364] The effective amount for therapeutic use depends on, for example, the mode of administration, the patient's weight and general health, and the judgment of the prescribing physician.The immunogenic composition may be administered in single or multiple doses, depending on the dosage and frequency and route of administration as required and tolerated by the patient.

[0365] In some cases, an effective amount of the immunogenic composition of the present invention is an amount that, when administered to an individual in one or more doses, effectively induces an antibody response (e.g., a neutralizing antibody response) in the individual to HCV. For example, antibodies to HCV (e.g., extracellular HCV) and / or to cells infected by HCV can be induced.

[0366] An effective amount of the immunogenic composition of the present invention can be an amount that, when administered to an individual in one or more doses, effectively induces a neutralizing antibody response against HCV of multiple genotypes (e.g., genotype 1; genotype 3, etc.). The neutralizing antibody response reduces the binding of HCV to one or more host receptors of HCV and inhibits HCV from entering cells.

[0367] In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the invention is an amount effective to induce a cytotoxic T lymphocyte (CTL) response (e.g., CD8 + For example, a CTL response against HCV infected cells can be induced.

[0368] In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the invention is an amount effective to induce helper T lymphocytes (e.g., CD4 T lymphocytes) against HCV in an individual when administered to the individual in one or more doses.+ T cells).

[0369] In some cases, the effective amount (e.g., therapeutically effective amount) of the immunogenic composition of the present invention is an amount that effectively induces an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response to HCV genotype 1 when applied to an individual at one or more doses. In some cases, the effective amount (e.g., therapeutically effective amount) of the immunogenic composition of the present invention is an amount that effectively induces an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response to HCV genotype 3 when applied to an individual at one or more doses. In some cases, the effective amount (e.g., therapeutically effective amount) of the immunogenic composition of the present invention is an amount that effectively induces an antibody response (e.g., a neutralizing antibody response) and / or a CTL response and / or a helper T cell response to HCV genotype 1 and HCV genotype 3 when applied to an individual at one or more doses. In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the invention is an amount that, when administered to an individual in one or more doses, effectively induces 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 invention is an amount that, when administered to an individual in one or more doses, effectively induces a CD8+ response against HCV genotypes 1-6. + In some cases, an effective amount (e.g., a therapeutically effective amount) of an immunogenic composition of the invention is one that is effective to induce CD4 T cell responses against HCV genotypes 1-6 when administered to an individual in one or more doses. + The amount of T cell response.

[0370] In mammalian subjects, the immunogenic compositions of the present invention are typically administered in an amount effective to elicit an immune response, such as a humoral immune response (e.g., an antibody response) and / or a CTL response. The effective amount of E1 / E2, E1 or E2 polypeptide used for immunization will vary and may typically be in the range of about 1 μg to 100 μg / 70kg patient, such as about 5 μg / 70kg patient to about 50 μg / 70kg patient. Significantly higher doses of HCV E1 / E2, E1 or E2 polypeptides (e.g., 10 mg to 100 mg or more) may be suitable for oral, nasal or topical routes of administration. In some cases, the dose of the immunogenic composition of the present invention comprises 4 μg to 100 μg of HCV E1 / E2 heterodimers. For example, in some cases, the dose of the immunogenic composition of the present invention comprises the following amount of HCV E1 / E2 heterodimer: 4μg to 5μg, 5μg to 10μg, 10μg to 15μg, 15μg to 20μg, 20μg to 25μg, 25μg to 30μg, 30μg to 40μg, 40μg to 50μg, 50μg to 60μg, 60μg to 70μg, 70μg to 80μg, 80μg to 90μg or 90μg to 100μg. In some cases, the dose of the immunogenic composition of the present invention comprises HCV E1 / E2 heterodimer in an amount of about 100μg to about 200μg.

[0371] In some cases, the amount of a given dose of a T cell epitope polypeptide ranges from 0.1 μg to 125 μg; for example, a suitable dose of a T cell epitope polypeptide ranges 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, if 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, if 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 a non-limiting example, if the immunogenic composition of the present invention includes 2 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, if the immunogenic composition of the present invention includes 2 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, if the immunogenic composition of the present invention includes 2 or more different T cell epitope polypeptides, the composition may include 6 μg of each different T cell epitope polypeptide.

[0372] In some cases, a single dose of an immunogenic composition of the invention comprises: a) HCV E1 / E2 heterodimers 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 E1 / E2 heterodimers); and b) two or more different T cell epitope polypeptides in an amount from 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 a non-limiting example, in some cases, a single dose of an immunogenic composition of the invention comprises: a) 15 μg E1 / E2 heterodimer; and b) 40 μg T cell epitope polypeptides (10 μg each of TP35-NS3, TP50C, TP27 and TP48).

[0373] In some cases, a dose of an immunogenic composition of the invention comprises an E1 / E2 heterodimer and a T cell epitope polypeptide, wherein 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 the immunogenic composition of the invention 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. If there are multiple different T cell epitope polypeptides in the immunogenic composition of the present invention, the molar ratio of the different T cell epitope polypeptides to the E1 / E2 heterodimer can be independently about 0.1:1 to about 0.2:1, about 0.1:1 to about 0.5:1, 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. As another example, the molar ratio of any given T cell epitope polypeptide to the E1 / E2 heterodimer is 1:1 to 25:1, such as 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 invention 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 invention 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 invention is 15:1.

[0374] As a non-limiting example, in some cases, the immunogenic composition of the invention comprises an E1 / E2 heterodimer and four different T cell epitope polypeptides, wherein the molar ratio of each T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is independently about 0.1:1 to about 25:1. As an example, in some cases, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide ("TP50C"), TP35-NS3 polypeptide ("TP35-NS3"), TP27 polypeptide ("TP27"), and 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; 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 composition of the present invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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 composition of the present invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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 composition of the present invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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 composition of the present invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimer; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide and 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, the immunogenic composition of the present invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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 invention comprises: i) E1 / E2 heterodimers; and ii) 4 different T cell epitope polypeptides, wherein the 4 different T cell epitope polypeptides are TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and TP48 polypeptide. As an example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP50C polypeptide, TP35-NS3 polypeptide, TP27 polypeptide, and 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 9:1. The amino acid sequences of 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 is 50 amino acids in length; the TP35-NS3 polypeptide comprises the following amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO:79) and is 35 amino acids in length; the TP27 polypeptide comprises the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO:103) and is 27 amino acids in length; the TP48 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO:136) and is 48 amino acids in length.

[0375] As a non-limiting example, in some cases, the immunogenic composition of the invention comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of each T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is independently about 0.1: 1 to about 25: 1. As an example, in some cases, the immunogenic composition of the invention 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 invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 0.5:1 to 1:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is from 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 1:1 to 5:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is from 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 5:1 to 10:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is from 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 10:1 to 25:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is from 10:1 to 25:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 1:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 3:1.As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9: 1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 9: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.1: 1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 0.1: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.3:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 0.3:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP48 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.5:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 0.5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; b) TP465 polypeptide and TP48 polypeptide, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 9:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; b) TP465 polypeptide and TP48 polypeptide, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9:1; and ii) the molar ratio of TP48 to E1 / E2 heterodimers is 3:1. The amino acid sequences of TP465 polypeptide and TP48 polypeptide are provided above.

[0376] As a non-limiting example, in some cases, the immunogenic composition of the invention comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of each T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is independently about 0.1: 1 to about 25: 1. As an example, in some cases, the immunogenic composition of the invention 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 invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 0.5:1 to 1:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is from 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 1:1 to 5:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is from 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 5:1 to 10:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is from 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 10:1 to 25:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is from 10:1 to 25:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 1:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 3:1.As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9: 1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 9: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.1: 1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 0.1: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.3:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 0.3:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.5:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 0.5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 9:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP65 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9:1; and ii) the molar ratio of TP65 to E1 / E2 heterodimers is 3:1. The amino acid sequences of TP465 polypeptides and TP65 polypeptides are provided above.

[0377] As a non-limiting example, in some cases, the immunogenic composition of the invention comprises an E1 / E2 heterodimer and two different T cell epitope polypeptides, wherein the molar ratio of each T cell epitope polypeptide to the E1 / E2 heterodimer in the composition is independently about 0.1: 1 to about 25: 1. As an example, in some cases, the immunogenic composition of the invention 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 invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 0.5:1 to 1:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is from 0.5:1 to 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is from 1:1 to 5:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is from 1:1 to 5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 5:1 to 10:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 5:1 to 10:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 10:1 to 25:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 10:1 to 25:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 1:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 1:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 3:1.As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9: 1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 9: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.1: 1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 0.1: 1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.3:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 0.3:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptides and TP156 polypeptides, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 0.5:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 0.5:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptide and TP156 polypeptide, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 3:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 9:1. As another example, in some cases, the immunogenic composition of the invention comprises: a) E1 / E2 heterodimers; and b) TP465 polypeptide and TP156 polypeptide, wherein: i) the molar ratio of TP465 to E1 / E2 heterodimers is 9:1; and ii) the molar ratio of TP156 to E1 / E2 heterodimers is 3:1. The amino acid sequences of TP465 polypeptide and TP156 polypeptide are provided above.

[0378] After the initial use, booster immunization can be carried out with identical immunogenic composition or different immunogenic compositions.In some cases, the subject method of inducing immune response relates to the initial use immunogenic composition of the present invention, then at least one booster is used, and relates to twice or more times (for example three times, four times or five times) booster in some cases.Initial use and booster use between or given booster use and subsequent booster use between interval can be about 1 week to about 12 weeks, for example 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 or about 10 weeks to about 12 weeks.Initial use and booster use between or given booster use and subsequent booster use between interval can be 4 months to 6 months or 6 months to 1 year.

[0379] In some cases, the immunogenic composition of the present invention of the first dose is applied for the first time, wherein the application is intramuscular administration; the immunogenic composition of the present invention of the second dose is applied for the second time, wherein the application is intranasal administration; the immunogenic composition of the present invention of the third dose is applied for the third time, wherein the application is intranasal administration. In some cases, about 1 week to about 12 weeks after the first dose, for example, 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, the second dose (first boost application) is applied. In some cases, about 1 week to about 12 weeks after the second dose, for example, 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, the third dose (second boost application) is applied.

[0380] In general, immunization can be accomplished by administering the immunogenic composition of the present invention by any suitable route, including oral, nasal (e.g., intranasal), nasopharyngeal, parenteral, intestinal, gastric, topical, transdermal, subcutaneous, intramuscular or intradermal administration of the composition. In some cases, the immunogenic composition of the present invention is administered intramuscularly. In some cases, the immunogenic composition of the present invention is administered subcutaneously. Immunization can be accomplished by topical or systemic administration of the immunogenic composition of the present invention in the form of tablets, solids, powders, liquids or aerosols with or without added excipients. The immunogenic composition of the present invention is in liquid form in many cases. The actual method of preparing parenterally administrable compositions is known or obvious to those skilled in the art, and is described in more detail in publications such as Remington's Pharmaceutical Science, 15th edition, Mack Publishing Company, Easton, Pa. (1980). In some cases, immunization is accomplished by intramuscular injection of the immunogenic composition of the present invention.

[0381] Individuals suitable for administration

[0382] Suitable subjects for administration of the immunogenic compositions of the invention include naive subjects (eg, subjects not infected with HCV and / or not administered an HCV vaccine). Suitable subjects for administration include humans.

[0383] Individuals suitable for administration of the immunogenic compositions of the compositions of the present invention include individuals at a higher risk of HCV infection than the general population, including, for example, intravenous drug users; individuals who are recipients or intended recipients of blood or blood products from another (donor) individual; individuals who are recipients or intended recipients of non-autologous cells, tissues or organs from another (donor) individual; health care workers; emergency medical and non-medical personnel (e.g., first responders; firefighters; emergency medical team personnel, etc.), etc.

[0384] Individuals suitable for administering the immunogenic compositions of the compositions of the present invention include individuals recently exposed to HCV or recently infected with HCV. For example, within about 24 hours to about 48 hours, about 48 hours to about 1 week, or about 1 week to about 4 weeks after possible or suspected exposure to HCV or infection with HCV, the subject immunogenic composition is administered to the individual.

[0385] Suitable subjects for administration of the immunogenic compositions of the present invention include subjects previously infected with HCV, subjects receiving HCV treatment, and cured subjects.

[0386] Individuals suitable for administering the immunogenic compositions of the compositions of the present invention include individuals diagnosed with HCV infection, and include individuals with chronic infection. In some cases, individuals diagnosed with HCV infection are treated with antiviral agents and the immunogenic compositions of the present invention. Suitable antiviral agents for treating HCV infection include, for example, ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide); interferon α (IFN-α) (wherein "IFN-α" includes IFN-α2a; IFN-α2b; IFN-α conjugated to poly(ethylene glycol) ("PEGylated IFN-α"), wherein the 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.

[0387] In some cases, individuals diagnosed with HCV infection receive treatment such as: 1) IFN-α + ribavirin; and an immunogenic composition of the invention; 2) IFN-α + ribavirin + HCV protease inhibitor (e.g., boceprevir or telaprevir); and an immunogenic composition of the invention; 3) Harvoni; and an immunogenic composition of the invention; 4) an inhibitor of HCV NS5B; and an immunogenic composition of the invention; 5) an inhibitor of HCV NS5A; and an immunogenic composition of the invention; or 6) an inhibitor of HCV NS5B + an inhibitor of HCV NS5A; and an immunogenic composition of the invention. Suitable antiviral agents for treating HCV infection include Sovaldi (Sofosbuvir; a nucleotide analog that acts as an NS5B polymerase inhibitor), alone or in combination with pegylated IFN-α and ribavirin; and Harvoni. Halvanir is a formulation containing 90 mg of ledipasvir and 400 mg of sofosbuvir. Leadipasvir is an inhibitor of HCV NS5A.

[0388] Examples of non-limiting aspects of the invention

[0389] The aforementioned aspects of the subject matter (including embodiments) may be beneficial alone or in combination with one or more other aspects or embodiments. Without limiting the foregoing description, certain non-limiting aspects of the invention are provided below. As will be apparent to one skilled in the art upon reading the present disclosure, each individually numbered aspect may be used or combined with any of the preceding or succeeding individually numbered aspects. This is intended to provide support for all combinations of these aspects, and is not limited to the combinations of aspects explicitly provided below:

[0390] Aspect 1. An immunogenic composition, comprising:

[0391] 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 polypeptide is selected from:

[0392] i) a TP35-NS3 T cell epitope polypeptide comprising the amino acid sequence:

[0393] KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), wherein 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, wherein the TP35-NS3 T cell epitope polypeptide has a length of 35 amino acids;

[0394] ii) a TP50C T cell epitope polypeptide comprising the amino acid sequence:

[0395] GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X 11 is S, T, H or A; X 12 A or G; X 13 is Q or K, wherein the TP50C T cell epitope polypeptide is 50 amino acids in length;

[0396] 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, wherein the TP27 T cell epitope polypeptide has a length of 27 amino acids; and

[0397] iv) a TP48 T cell epitope polypeptide comprising the amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DA X 14 X 15 X 16 VX 17 X 18 X 19 L (SEQ ID NO: 134), 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; X 10 is V or I; X11 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; X15 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, wherein the TP48 T cell epitope polypeptide is 48 amino acids in length; and

[0398] b1) 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 comprising a saponin; or

[0399] 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 polypeptide is selected from:

[0400] i) a TP65 polypeptide comprising the amino acid sequence:

[0401] TPIDTTIMAKNEVFCVDPX6KGGRKPARLIVYPDLGVRVCEKMALYDV VQKLPQAVMGX7SYGFQYS (SEQ ID NO: 152), wherein X6 is E, T or V, and X7 is S, A or P, wherein the TP65 polypeptide is 65 amino acids in length;

[0402] ii) a TP50C T cell epitope polypeptide comprising the amino acid sequence:

[0403] GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X11 is S, T, H or A; X 12 is A or G; X13 is Q or K, wherein the TP50C T cell epitope polypeptide has a length of 50 amino acids;

[0404] iii) a TP240 T cell epitope polypeptide comprising the amino acid sequence:

[0405] 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, wherein the TP240 polypeptide has a length of 240 amino acids; and

[0406] iv) a TP48 T cell epitope polypeptide comprising the amino acid sequence:

[0407] X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19L (SEQ ID NO: 134), 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; 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 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, wherein the TP48 T cell epitope polypeptide is 48 amino acids in length; and

[0408] 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 comprising a saponin;

[0409] or

[0410] 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 polypeptide is selected from:

[0411] i) a TP35-NS3 T cell epitope polypeptide comprising the following amino acid sequence:

[0412] KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO: 73), wherein 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; X8 is K or R, wherein the TP35-NS3 T cell epitope polypeptide has a length of 35 amino acids;

[0413] ii) a TP50C T cell epitope polypeptide comprising the amino acid sequence:

[0414] GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X11 is S, T, H or A; X 12 is A or G; and X 13 is Q or K, wherein the TP50C T cell epitope polypeptide is 50 amino acids in length;

[0415] 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; X8 is T, R or S, wherein the TP27 T cell epitope polypeptide has a length of 27 amino acids; and

[0416] iv) a TP48 T cell epitope polypeptide comprising the amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DA X 14 X 15 X 16 VX 17 X 18 X 19 L (SEQ ID NO: 134), 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; 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 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, wherein the TP48 T cell epitope polypeptide is 48 amino acids in length;

[0417] v) a TP240 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:

[0418] SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 157), wherein the TP240 T cell epitope polypeptide has a length of 240 amino acids;

[0419] vi) a TP65 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:

[0420] TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVV QKLPQAVMGSSYGFQYS (SEQ ID NO: 153), wherein the TP65 T cell epitope polypeptide has a length of 65 amino acids;

[0421] vii) a TP156 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:

[0422] KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), wherein the TP156 T cell epitope polypeptide has a length of 156 amino acids;

[0423] viii) a TP465 T cell epitope polypeptide comprising Figures 11A-11C 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 any of the amino acid sequences shown in , wherein the TP465 T cell epitope polypeptide is 465 amino acids in length;

[0424] ix) a TP23 T cell epitope polypeptide comprising the following amino acid sequence: DVVVX1X2TDALMTGX3TGDFDSVID (SEQ ID NO: 89), wherein X1 is V or C; X2 is A or S; X3 is F or Y; wherein the TP23 polypeptide is 23 amino acids in length;

[0425] x) TP35-NS4 T cell epitope polypeptide comprising 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; wherein the TP35-NS4 polypeptide is 35 amino acids in length;

[0426] xi) a TP42 T cell epitope polypeptide comprising the 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; X 10 A, K or S; X 11 Is K, Q or A; X 12 is T, R or S; X 13 is G or S; wherein the TP42 polypeptide is 42 amino acids in length;

[0427] xii) TP45 T cell epitope polypeptide comprising the amino acid sequence: X1X2AVAX3YRGX4DVX5X6IPX7X8GDVVVX9X 10 TDALMTGX 11 TGDFDSVIDX 12 X 13 X14 (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; X 10 A or S; X 11 is F or Y; X 12 is C or K; X 13 is N or K; and X 14 is V or K; and wherein the TP45 T cell epitope polypeptide is 45 amino acids in length;

[0428] xiii) a TP33 T cell epitope polypeptide comprising the amino acid sequence: HSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 143), wherein 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; wherein the TP33 polypeptide is 33 amino acids in length;

[0429] xiv) a TP42-2 polypeptide comprising the following amino acid sequence: KGGRHLIFCHSKKKCDELAX1X2LX3X4X5GX6NAVAYYRGLDVSX7IP (SEQ ID NO: 148), wherein 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; wherein the T42-2 polypeptide is 42 amino acids in length;

[0430] xv) a TP29 polypeptide comprising Fig.12 The TP29 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP29 polypeptide is 29 amino acids in length;

[0431] xvi) a TP50-NS2 polypeptide comprising Fig.12 an amino acid sequence of TP50-NS2 having at least 50% amino acid sequence identity, wherein the TP50-NS2 polypeptide is 50 amino acids in length;

[0432] xvii) a TP52 polypeptide comprising Fig.12 The TP25 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP52 polypeptide is 52 amino acids in length;

[0433] xviii) a TP70 polypeptide comprising Fig.12The TP70 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP70 polypeptide is 70 amino acids in length;

[0434] xix) TP100 polypeptide comprising Fig.12 The TP100 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP100 polypeptide is 100 amino acids in length;

[0435] xx) TP171 polypeptide comprising Fig.12 The TP171 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP171 polypeptide is 171 amino acids in length;

[0436] xxi) a TP228 polypeptide comprising Fig.12 The TP228 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP228 polypeptide is 228 amino acids in length;

[0437] xxii) A TP553 polypeptide comprising Fig.12 The TP553 amino acid sequence shown has an amino acid sequence with at least 50% amino acid sequence identity, wherein the TP553 polypeptide is 553 amino acids in length;

[0438] xxiii) a TP778 polypeptide comprising Fig.12 An amino acid sequence having at least 50% amino acid sequence identity to the TP778 amino acid sequence shown, wherein the TP778 polypeptide is 778 amino acids in length; and

[0439] xxiv) TP1987 polypeptide comprising Fig.12 An amino acid sequence having at least 50% amino acid sequence identity to the TP1987 amino acid sequence shown, wherein the TP1987 polypeptide is 1987 amino acids in length; and

[0440] b3) A second generation lipid adjuvant (SLA), which is a toll-like receptor 4 (TLR4) agonist, formulated in either: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

[0441] Aspect 2. The immunogenic composition according to aspect 1, wherein SLA has the following structure:

[0442]

[0443] Aspect 3. The immunogenic composition according to aspect 1 or aspect 2, wherein the liposome composition comprising saponin comprises a sterol.

[0444] Aspect 4. The immunogenic composition according to Aspect 3, wherein the saponin is complexed with a sterol.

[0445] Aspect 5. The immunogenic composition according to Aspect 3 or Aspect 4, wherein the sterol is cholesterol.

[0446] Aspect 6. The immunogenic composition according to any one of aspects 1 to 5, wherein the liposome composition comprises a phospholipid.

[0447] Aspect 7. An immunogenic composition according to Aspect 6, wherein the phospholipid is selected from DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DLPG, DMPG, DPPG, DSPG, DOPG, DSTAP, DPTAP, DSPE, DPPE, DMPE and DLPE.

[0448] Aspect 8. The immunogenic composition according to any one of aspects 1 to 7, wherein the saponin is QS21, QS17, QS7, synthetic QS21 (SQS21), Quil-A, QS21-Api and QS21-Xyl.

[0449] Aspect 9. An immunogenic composition according to Aspect 1 or Aspect 2, wherein the stable oil-in-water emulsion comprises an aqueous phase and an oil phase, wherein the aqueous phase comprises SLA, and wherein 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.

[0450] Aspect 10. The immunogenic composition according to aspect 9, wherein the aqueous phase comprises poloxamer 188 and glycerol.

[0451] Aspect 11. The immunogenic composition according to aspect 9 or aspect 10, wherein the oil phase comprises egg phosphatidylcholine or dimyristoylphosphatidylcholine (DMPC) or DOPC.

[0452] Aspect 12. The immunogenic composition according to any one of Aspects 9-11, comprising a surfactant.

[0453] Aspect 13. The immunogenic composition according to Aspect 12, wherein the surfactant is Pluronic F68.

[0454] Aspect 14. The immunogenic composition according to any one of Aspects 1 to 13, wherein:

[0455] a) the TP35-NS3 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the following amino acid sequence:

[0456] KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK(SEQ ID NO:79);

[0457] 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:

[0458] GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPG YP (SEQ ID NO:87);

[0459] c) the TP27 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103); and

[0460] d) the TP48 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity to the following amino acid sequence:

[0461] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136).

[0462] Aspect 15. The immunogenic composition according to any one of aspects 1 to 13, wherein the fusion polypeptide comprises, from N-terminus to C-terminus:

[0463] a) TP35-NS3 T cell epitope polypeptide;

[0464] b) TP27 T cell epitope polypeptide;

[0465] c) TP48 T cell epitope polypeptide; and

[0466] d) TP50C T cell epitope polypeptide.

[0467] Aspect 16. The immunogenic composition according to any one of aspects 1 to 15, comprising a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide or an HCV E1 / E2 heterodimeric polypeptide.

[0468] Aspect 17. The immunogenic composition according to Aspect 16, wherein the HCV E1 and / or E2 polypeptide is from HCV genotype 1.

[0469] Aspect 18. The immunogenic composition according to Aspect 16, wherein the HCV E1 and / or E2 polypeptide is from HCV genotype 2.

[0470] Aspect 19. The immunogenic composition according to Aspect 16, wherein the HCV E1 and / or E2 polypeptide is from HCV genotype 3.

[0471] Aspect 20. An immunogenic composition according to Aspect 16, wherein the HCV E1 and / or E2 polypeptides are 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.

[0472] Aspect 21. An immunogenic composition according to any one of aspects 16 to 20, comprising an HCV E1 / E2 heterodimeric polypeptide and one or more T cell epitope polypeptides.

[0473] Aspect 22. The immunogenic composition according to Aspect 21, wherein the molar ratio of one or more T cell epitope polypeptides to the HCVE1 / E2 heterodimeric polypeptide is from 0.1:1 to 25:1.

[0474] Aspect 23. An immunogenic composition according to aspect 21, wherein the composition comprises two or more T cell epitope polypeptides, and wherein the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:1.

[0475] Aspect 24. The immunogenic composition according to aspect 23, wherein the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 2:1 to 15:1.

[0476] Aspect 25. An immunogenic composition according to aspect 23, wherein the composition comprises four T cell epitope polypeptides, and wherein the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:1.

[0477] Aspect 26. The immunogenic composition according to Aspect 25, wherein the molar ratio of each of the four T cell epitope polypeptides to the HCVE1 / E2 heterodimeric 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, 10:1 to 25:1.

[0478] Aspect 27. The immunogenic composition according to Aspect 25, wherein the molar ratio of each of the four T cell epitope polypeptides to the HCVE1 / E2 heterodimeric polypeptide is independently 0:1:1, 0.3:1, 0.5:1 or 1:1.

[0479] Aspect 28. The immunogenic composition according to aspect 26, wherein the molar ratio of one or more of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is 3:1.

[0480] Aspect 29. The immunogenic composition according to aspect 26, wherein the molar ratio of one or more of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is 9:1.

[0481] Aspect 30. The immunogenic composition according to any one of aspects 25 to 29, wherein the four T cell epitope polypeptides are TP50C polypeptide, TP-35 NS3 polypeptide, TP27 polypeptide and TP48 polypeptide.

[0482] Aspect 31. The immunogenic composition according to aspect 30, wherein:

[0483] i) The TP50C polypeptide comprises the following amino acid sequence:

[0484] GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPG YP (SEQ ID NO: 87), and is 50 amino acids in length;

[0485] ii) the TP35-NS3 polypeptide comprises the following amino acid sequence:

[0486] KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79), and is 35 amino acids in length;

[0487] iii) the TP27 polypeptide comprises the following amino acid sequence:

[0488] LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103), and is 27 amino acids in length; and

[0489] iv) the TP48 polypeptide comprises the following amino acid sequence:

[0490] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), and is 48 amino acids in length.

[0491] Aspect 32. An immunogenic composition according to aspect 23, wherein the composition comprises two T cell epitope polypeptides, and wherein the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:1.

[0492] Aspect 33. An immunogenic composition according to Aspect 32, wherein the molar ratio of each of the two T cell epitope polypeptides to the HCVE1 / E2 heterodimeric 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, 10:1 to 25:1.

[0493] Aspect 34. The immunogenic composition according to Aspect 32, wherein the molar ratio of each of the two T cell epitope polypeptides to the HCVE1 / E2 heterodimeric polypeptide is independently 0:1:1, 0.3:1, 0.5:1 or 1:1.

[0494] Aspect 35. The immunogenic composition according to Aspect 32, wherein the molar ratio of one or more of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is 3:1.

[0495] Aspect 36. The immunogenic composition according to Aspect 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.

[0496] Aspect 37. The immunogenic composition according to any one of aspects 32 to 36, wherein the two T cell epitope polypeptides are:

[0497] a) TP465 polypeptide and TP48 polypeptide;

[0498] b) a TP465 polypeptide and a TP65 polypeptide; or

[0499] c) TP465 polypeptide and TP156 polypeptide.

[0500] Aspect 38. An immunogenic composition according to any one of Aspects 1-37, further comprising an adjuvant selected from the group consisting of MF59, alum, CpG oligonucleotides, cyclic dinucleotides, 3'-O-deacylated-4'-monophosphoryl lipid A (MPL), aluminum hydroxide, aluminum phosphate, AS01, AS02, AS03, AS04, 3M-052, and combinations thereof.

[0501] Aspect 39. A method of inducing an immune response in an individual against hepatitis C virus (HCV), the method comprising administering to the individual an effective amount of the composition of any one of aspects 1-38.

[0502] Aspect 40. The method according to aspect 39, comprising:

[0503] a) administering a first dose of the composition for the first time; and

[0504] b) administering a second dose of the composition a second time.

[0505] Aspect 41. The method according to aspect 40, wherein the second time is within a time period of about 1 week to about 6 months from the first time.

[0506] Aspect 42. The method according to any one of aspects 39 to 41, wherein the administration is intramuscular administration.

[0507] Aspect 43. The method according to any one of aspects 39 to 41, wherein the administration is subcutaneous administration.

[0508] Aspect 44. A container comprising the immunogenic composition according to any one of aspects 1-38.

[0509] Aspect 45. The container according to aspect 44, wherein the container and the composition are sterile.

[0510] Aspect 46. The container according to Aspect 44 or Aspect 45, wherein the container is a syringe.

[0511] Example

[0512] The following examples are provided to provide those of ordinary skill 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 to represent that the following experiments are all or the only experiments performed. Efforts have been made to ensure the accuracy of the numbers used (e.g., amounts, temperatures, etc.), but some experimental errors and deviations should be taken into account. 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 pressure. Standard abbreviations may be used, such as bp, base pair; kb, kilobase; pl, picoliter; s or sec, second; min, minute; h or hr, hour; aa, amino acid; kb, kilobase; bp, base pair; nt, nucleotide; im, intramuscular; ip, intraperitoneal; sc, subcutaneous; and the like.

[0513] Example 1

[0514] Here, when the mixture of E1E2 and 4TP was adjuvanted with SLA-LSQ or with SLA-SE, in addition to strong CD4 T cell and humoral responses against E1E2, strong CD8 T cell and extremely strong CD4 T cell responses against 4TP were reported.

[0515] Experimental Design and Methods

[0516] A mixture of E1E2 and 4TP (including TP50-C, TP35-NS3, TP27 and TP48) was used as adjuvant: (i) Alum-OH / MPLA (InvivoGen; San Diego, CA 92121 USA); (ii) AddaAS03 (InvivoGen); (iii) SLA-LSQ (IDRI); or (iv) SLA-SE (IDRI) for intramuscular immunization of CB6-F1 mice. Three injections were performed on days 0, 14 and 42, and mice were euthanized on day 56. Blood was collected on day 0 (before immunization) and day 56 (two weeks after the third immunization). Serum was extracted and inactivated, stored, and used for E1E2-specific enzyme-linked immunosorbent assay (ELISA) and neutralization assays at appropriate times. Spleens were collected on day 56, splenocytes were isolated, and used for 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): 6949-6956. Short peptides covering E1E2 and 4TP were chemically synthesized and assembled in two separate pools and used to re-stimulate splenocytes in vitro.

[0517] The amino acid sequences of the four TPs are as follows:

[0518] TP50-C:

[0519] GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPGYP(SEQ ID NO:87);

[0520] TP35-NS3:KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO:79);

[0521] TP27:LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103);

[0522] TP48:

[0523] ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136).

[0524] result

[0525] To evaluate the humoral immunogenicity of the adjuvanted HCV rE1E2-4TP vaccine, the levels of E1E2-specific IgG in mouse sera were compared ( Figure 5 ) and neutralization activity of diluted sera after vaccination against HCV pseudoparticles ( Figure 6 The results showed that the IDRI adjuvants (SLA-LSQ and SLA-SE) had equal or higher effectiveness compared to Alum-OH / MPLA and AddaAS03.

[0526] Figure 5 .E1E2-specific IgG levels in sera of post-vaccination mice collected on day 56 after subtracting the levels in sera of pre-vaccination mice collected on day 0.

[0527] Figure 6 Diluted post-vaccination mouse sera collected on day 56 were used to neutralize HCV pseudoparticles expressing E1E2 (data were normalized to pre-vaccination mouse sera collected on day 0).

[0528] To assess T cell responses, the presence of polyfunctional T cells secreting IFN-γ, TNF-α, and / or IL-2 was investigated after in vitro restimulation of splenocytes. Flow cytometry data showed that vaccines containing IDRI adjuvant induced strong and extremely strong CD4 T cell responses against E1E2 and 4TP, respectively. Notably, IDRI adjuvant induced strong 4TP-specific CD8 T cell responses in preclinical animal studies ( Figure 7A-7B ). CD8 + T cells secrete IFN-γ and TNF-α ( Fig. 7A ). CD4 + T cells express IFN-γ and TNF-α ( Fig. 7A ) and IFN-γ and IL-2 ( Figure 7B ) produced all three cytokines (IFN-γ, TNF-α, and IL-2). The data showed that HCV vaccines induced humoral and cellular immune responses and could induce strong CD8 T cell responses when adjuvanted with SLA-LSQ or SLA-SE.

[0529] Figure 7A-7B The E1E2-4TP mixture with SLA-LSQ and SLA-SE as adjuvants can induce CD8 + T cell generation ( Fig. 7A ) and CD4 that produce IFN-γ, TNF-α, and IL-2 + T cell generation ( Fig. 7A and 7B ).

[0530] Example 2

[0531] Methods and Materials

[0532] CB6-F1 mice were immunized intramuscularly with a mixture of adjuvanted E1E2 and TP (the same 4 TPs as in Example 1). Three injections were performed on days 0, 14, and 42. Mice were euthanized on day 56 and spleens were collected. 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 a full-length single TP (rather than with a peptide pool containing short peptides covering all 4TPs). The presence of multifunctional T cells expressing IFN-γ, TNF-α, and / or IL-2 was studied in an intracellular cytokine assay using flow cytometry.

[0533] result

[0534] Data such as Figures 13A-13B Flow cytometry data showed that restimulation of splenocytes with TP48 induced a strong CD4 + T cell response. This response was highest in TP, followed by TP35-NS3, TP50-C, and finally TP27. Among TP, TP27 induced CD4 T cell response in the SLA-SE group. Multifunctional CD4 T cells were able to express IFN-γ and TNF-α ( Fig.13A ) and IFN-γ and IL-2 ( Fig. 13B ) produce all three cytokines. Regarding CD8 T cells, TP48 induces multifunctional CD8 + T cells ( Fig.14A ), the CD8 + T cells express IFN-γ and TNF-α, but not IL-2 ( Fig. 14B ). This HCV vaccine contains humoral and cellular components and can induce strong CD8 T cell responses when adjuvanted with SLA-LSQ or SLA-SE.

[0535] Although the present invention has been described with reference to specific embodiments of the present invention, it will be appreciated by those skilled in the art that various changes and replacement of equivalents may be made without departing from the true spirit and scope of the present invention. In addition, many modifications may be made to adapt specific circumstances, materials, material compositions, methods, one or more method steps to the purpose, spirit and scope of the present invention. All of these modifications are intended to be within the scope of the claims appended hereto.

Claims

1. An immunogenic composition, comprising: a) 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 selected from: i) a TP35-NS3 T cell epitope polypeptide comprising the amino acid sequence: KSTKVPX1AYX2X3QGYX4VLVLNPSVAATLGFGX5X6X7SX8 (SEQ ID NO:73), wherein 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, wherein the TP35-NS3 T cell epitope polypeptide is 35 amino acids in length; ii) a TP50C T cell epitope polypeptide comprising the amino acid sequence: GVYX1LPRRGPRLGVRX2TRKX3SERSQPRGRRQX4IPKX5X6X7X8X9GX 10 X 11 WX 12 X 13 PGYP (SEQ ID NO: 80), wherein 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; X 10 is R or K; X 11 is S, T, H or A; X 12 is A or G; and X 13 is Q or K, wherein the TP50C T cell epitope polypeptide is 50 amino acids in length; 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, wherein the TP27 T cell epitope polypeptide is 27 amino acids in length; and iv) a TP48 T cell epitope polypeptide comprising the amino acid sequence: X1X2X3RHX4GX5X6EGX7X8QWMNRLIAFASRGNHVX9PTHYX 10 X 11 X 12 X 13 DAX 14 X 15 X 16 VX 17 X 18 X 19 L (SEQ ID NO: 134), 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; 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 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, wherein the TP48 T cell epitope polypeptide is 48 amino acids in length; v) a TP240 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: SYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTVTTGAPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALGTEGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLRGMGLNAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTGDFDSVIDCNVAVTQT (SEQ ID NO: 157), wherein the TP240 T cell epitope polypeptide has a length of 240 amino acids; vi) a TP65 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: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVV QKLPQAVMGSSYGFQYS (SEQ ID NO: 153), wherein the TP65 T cell epitope polypeptide has a length of 65 amino acids; vii) a TP156 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: KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), wherein the TP156 T cell epitope polypeptide has a length of 156 amino acids; and 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 the amino acid sequence depicted in any one of Figures 11A-11C, wherein the TP465 T cell epitope polypeptide is 465 amino acids in length; and b) A second generation lipid adjuvant (SLA), which is a toll-like receptor 4 (TLR4) agonist, formulated in either: i) a stable emulsion; or ii) a liposomal composition comprising saponin.

2. The immunogenic composition of claim 1, wherein the SLA has the following structure:

3. The immunogenic composition of claim 1 or claim 2, wherein the saponin-containing liposome composition comprises a sterol.

4. The immunogenic composition of claim 3, wherein the saponin is complexed with a sterol.

5. The immunogenic composition of claim 3 or claim 4, wherein the sterol is cholesterol.

6. The immunogenic composition of any one of claims 1-5, wherein the liposome composition comprises a phospholipid.

7. The immunogenic composition of claim 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.

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

9. The immunogenic composition of claim 1 or claim 2, wherein the stable oil-in-water emulsion comprises an aqueous phase and an oil phase, wherein the aqueous phase comprises SLA, and wherein 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.

10. The immunogenic composition of claim 9, wherein the aqueous phase comprises poloxamer 188 and glycerol.

11. An immunogenic composition according to claim 9 or claim 10, wherein the oil phase comprises egg phosphatidylcholine or dimyristoylphosphatidylcholine (DMPC).

12. The immunogenic composition according to any one of claims 9 to 11, comprising a surfactant.

13. The immunogenic composition of claim 12, wherein the surfactant is Pluronic F68.

14. The immunogenic composition according to any one of claims 1 to 13, wherein: A) The composition comprises a TP35-NS3 T cell epitope polypeptide, a TP50C T cell epitope polypeptide, a TP27 T cell epitope polypeptide and a TP48 polypeptide, and wherein: a) the TP35-NS3 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the following amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK(SEQ ID NO:79); b) the TP50C T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the following amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPG YP (SEQ ID NO:87); c) the TP27 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103); and d) the TP48 T cell epitope polypeptide comprises an amino acid sequence having at least 80% amino acid sequence identity with the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL(SEQ ID NO:136); or B) The composition comprises a TP156 T cell epitope polypeptide, a TP465 T cell epitope polypeptide, a TP48 T cell epitope polypeptide and a TP65 polypeptide, and wherein: a) the TP156 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 to the following sequence: KFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFL (SEQ ID NO: 160), wherein the TP156 T cell epitope polypeptide has a length of 156 amino acids; b) the TP465 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 to the amino acid sequence shown in any one of Figures 11A-11C, wherein the TP465 T cell epitope polypeptide is 465 amino acids in length; c) the TP48 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 to the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), wherein the TP48 polypeptide is 48 amino acids in length; and d) the TP65 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 to: TPIDTTIMAKNEVFCVDPEKGGRKPARLIVYPDLGVRVCEKMALYDVV QKLPQAVMGSSYGFQYS (SEQ ID NO: 153), wherein the TP65 T cell epitope polypeptide has a length of 65 amino acids.

15. The immunogenic composition according to any one of claims 1 to 13, wherein the fusion polypeptide comprises, from N-terminus to 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.

16. The immunogenic composition of any one of claims 1-15, comprising a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1 / E2 heterodimeric polypeptide.

17. The immunogenic composition of claim 16, wherein the HCV E1 and / or E2 polypeptides are from HCV genotype 1.

18. The immunogenic composition of claim 16, wherein the HCV E1 and / or E2 polypeptides are from HCV genotype 2.

19. The immunogenic composition of claim 16, wherein the HCV E1 and / or E2 polypeptides are from HCV genotype 3.

20. The immunogenic composition of claim 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.

21. The immunogenic composition of any one of claims 16-20, comprising an HCV E1 / E2 heterodimeric polypeptide and one or more T cell epitope polypeptides.

22. The immunogenic composition of claim 21, wherein the molar ratio of the one or more T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is from 0.1:1 to 25:

1.

23. The immunogenic composition of claim 21, wherein the composition comprises two or more T cell epitope polypeptides, and wherein the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:

1.

24. The immunogenic composition of claim 23, wherein the molar ratio of each of the two or more T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 2:1 to 15:

1.

25. The immunogenic composition of claim 23, wherein the composition comprises four T cell epitope polypeptides, and wherein the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:

1.

26. The immunogenic composition of claim 25, wherein the molar ratio of each of the four T cell epitope polypeptides to the HCV E1 / E2 heterodimeric 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, 10:1 to 25:

1.

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

1.

28. The immunogenic composition of claim 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.

29. The immunogenic composition of claim 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.

30. The immunogenic composition according to any one of claims 25-29, wherein the four T cell epitope polypeptides are TP50C polypeptide, TP-35NS3 polypeptide, TP27 polypeptide and TP48 polypeptide.

31. The immunogenic composition of claim 30, wherein: i) The TP50C polypeptide comprises the following amino acid sequence: GVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRSEGRSWAQPG YP (SEQ ID NO: 87), and is 50 amino acids in length; ii) the TP35-NS3 polypeptide comprises the following amino acid sequence: KSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSK (SEQ ID NO: 79), and is 35 amino acids in length; iii) the TP27 polypeptide comprises the following amino acid sequence: LEQIKGGRHLIFCHSKKKCDELAAKLR (SEQ ID NO: 103), and is 27 amino acids in length; and iv) the TP48 polypeptide comprises the following amino acid sequence: ILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQIL (SEQ ID NO: 136), and is 48 amino acids in length.

32. The immunogenic composition of claim 23, wherein the composition comprises two T cell epitope polypeptides, and wherein the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0.1:1 to 25:

1.

33. The immunogenic composition of claim 32, wherein the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimeric 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, 10:1 to 25:

1.

34. The immunogenic composition of claim 32, wherein the molar ratio of each of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimeric polypeptide is independently 0:1:1, 0.3:1, 0.5:1 or 1:

1.

35. The immunogenic composition of claim 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.

36. The immunogenic composition of claim 32, wherein the molar ratio of one or more of the two T cell epitope polypeptides to the HCV E1 / E2 heterodimer polypeptide is 9:

1.

37. The immunogenic composition according to any one of claims 32-36, wherein the two T cell epitope polypeptides are: a) TP465 polypeptide and TP48 polypeptide; b) a TP465 polypeptide and a TP65 polypeptide; or c) TP465 polypeptide and TP156 polypeptide.

38. The immunogenic composition of any one of claims 1-37, further comprising an adjuvant selected from the group consisting of MF59, alum, CpG oligonucleotides, cyclic dinucleotides, 3'-O-deacylated-4'-monophosphoryl lipid A (MPL), aluminum hydroxide, aluminum phosphate, AS01, AS02, AS03, AS04, 3M-052, and combinations thereof.

39. A method of inducing an immune response in an individual to hepatitis C virus (HCV), the method comprising administering to the individual an effective amount of the composition of any one of claims 1-38.

40. The method of claim 39, comprising: a) administering a first dose of the composition for the first time; and b) administering a second dose of the composition a second time.

41. The method of claim 40, wherein the second time is a time period of about 1 week to about 6 months from the first time.

42. The method of any one of claims 39-41, wherein the administration is intramuscular administration.

43. The method of any one of claims 39-41, wherein the administration is subcutaneous administration.

44. A container comprising the immunogenic composition of any one of claims 1-38.

45. The container of claim 44, wherein the container and the composition are sterile.

46. ​​The container of claim 44 or claim 45, wherein the container is a syringe.

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