Hepatitis C virus immunogenic compositions and methods of use thereof
The present disclosure provides immunogenic compositions comprising: a) hepatitis C virus (HCV) E1E2 heterodimers, HCV E2, or HCV E1; and b) an adjuvant, where the adjuvant is a cyclic dinucleotide or an archaeosome. The present disclosure provides methods of inducing an immune response in an individual to HCV, the methods comprising administering to an individual an effective amount of an immunogenic composition of the present disclosure.
1. An immunogenic composition comprising:
a) a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1/E2 heterodimer; and
b) a cyclic dinucleotide (CDN).
2. The immunogenic composition of claim 1 , wherein the CDN is fluorinated.
3. The immunogenic composition of claim 2 , wherein the CDN is 2′-F-c-di-GMP.
4. The immunogenic composition of claim 1 , wherein the CDN is of Formula (I):
wherein:
A is S or O;
X is S, N, O, CH 2 ;
Y, Y′ is NH, CH 2 , O;
Z, Z′ is NH, CH 2 , O;
R1 represents hydrogen or NH 2 which may be substituted;
R2 is hydrogen or absent;
R3 represents NH 2 , O, OH, H, or a halogen;
R4 represents hydrogen, halogen, or a straight or branched C 1 -C 6 alkyl group which may optionally be substituted;
R5 represents hydrogen, OH or a straight or branched C 1 -C 6 alkyl chain or C 1 -C 6 straight or branched alkoxy chain which may optionally be substituted;
is a single or double bond;
or conjugates thereof, and salts or solvates thereof.
5. The immunogenic composition of claim 4 , wherein the CDN is c-diGMP, c-diAMP, c-dilMP, c-dXMP, c-GpAp, c-Gplp, c-GpXp, c-Aplp, c-ApXp, or c-lpXp.
6. The immunogenic composition of claim 1 , wherein the CDN is cyclic-GMP-AMP (cGAMP).
7. The immunogenic composition of claim 6 , wherein the cGAMP is 2′3′-cGAMP, 2′2-cGAMP, 3′2′-cGAMP or 3′3′-GAMP.
8. The immunogenic composition of claim 1 , wherein the HCV E1 polypeptide, the HCV E2 polypeptide, or one or both chains of the HCV E1/E2 heterodimer comprises a covalently linked T-cell epitope polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2.
9. The immunogenic composition of claim 1 , comprising a T-cell epitope polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2, wherein the T-cell epitope polypeptide is not covalently linked to the HCV E1E2 heterodimer, the HCV E1 polypeptide, or the HCV E2 polypeptide.
10. The immunogenic composition of claim 8 , wherein the T-cell epitope polypeptide comprises an amino acid sequence having at least 20% amino acid sequence identity to the amino acid sequence of one of TP29 (SEQ ID NO: 85), TP50 (SEQ ID NO: 86), TP52 (SEQ ID NO: 87), TP70 (SEQ ID NO: 88), TP100 (SEQ ID NO: 89), TP171 (SEQ ID NO: 90), TP228 (SEQ ID NO: 91), TP553 (SEQ ID NO: 92), TP778 (SEQ ID NO: 93), and TP1985 (SEQ ID NO: 94).
11. A method of inducing an immune response to HCV in an individual, the method comprising administering to the individual an effective amount of the immunogenic composition of claim 1 .
12. The method of claim 11 , wherein said administering is via intramuscular administration, intranasal administration, subcutaneous administration, or a combination thereof.
13. The method of claim 11 , wherein said administering comprises a prime and a boost.
14. An immunogenic composition comprising:
a) one or more nucleic acids comprising nucleotide sequences encoding a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1/E2 heterodimer; and
b) a cyclic dinucleotide.
15. A method of inducing an immune response to HCV in an individual, the method comprising administering to the individual an effective amount of the composition of claim 14 .
16. An immunogenic composition comprising:
a) a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1/E2 heterodimer, or one or more nucleic acids comprising nucleotide sequences encoding the HCV E1 polypeptide, the HCV E2 polypeptide, or the HCV E1/E2 heterodimer; and
b) an archaeosome comprising at least one polar synthetic lipid, wherein the at least one polar synthetic lipid comprises at least one carbohydrate or anionic group linked by covalent bonding to at least one free hydroxyl group of an archaeal core lipid.
17. The immunogenic composition of claim 16 , wherein the archaeal core lipid is archaeol (2,3-di-O-diphytanyl-sn-glycerol) or caldarchaeol (2,2′,3,3′-tetra-O-dibiphytanyl-sn-diglycerol).
18. A method of inducing an immune response to HCV in an individual, the method comprising administering to the individual an effective amount of the immunogenic composition of claim 16 .