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. A method of inducing an immune response to an antigen in an individual, the method comprising administering to the individual:
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 (CDN).
2. The method of claim 1 , wherein the CDN is fluorinated.
3. The method of claim 2 , wherein the CDN is 2′-F-c-di-GMP.
4. The method 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 method 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 method of claim 5 , wherein the CDN is cyclic-GMP-AMP (cGAMP).
7. The method of claim 6 , wherein the cGAMP is 2′3′-cGAMP, 2′2-cGAMP, 3′2′-cGAMP or 3′3′-GAMP.
8. The method of claim 1 , wherein the one or more nucleic acids comprise nucleotide sequences encoding an HCV E1/E2 heterodimer.
9. The method of claim 8 , wherein:
a) the HCV E2 polypeptide is derived from an HCV of genotype 1, 2, 3, 4, 5, 6, or 7; and
b) the HCV E1 polypeptide is derived from an HCV of genotype 1, 2, 3, 4, 5, 6, or 7.
10. The method of claim 1 , wherein the one or more nucleic acids are one or more RNA molecules.
11. The method of claim 10 , wherein the one or more RNA molecules are formulated with a liposome.
12. The method of claim 1 , wherein said administering is via intramuscular administration, intranasal administration, subcutaneous administration, or a combination thereof.
13. The method of claim 1 , wherein said administering is intranasal administration.
14. The method of claim 1 , wherein said administering comprises a prime and a boost.
15. The method of claim 1 , wherein the individual is a human.
16. The method of claim 15 , wherein the individual is at greater risk than the general population of becoming infected with HCV.
17. The method of claim 1 , wherein the one or more nucleic acids are one or more recombinant expression vectors.
18. The method of claim 17 , wherein the one or more recombinant expression vectors are recombinant viral vectors.
19. The method of claim 18 , wherein the one or more recombinant viral vectors are packaged into viral particles.