Hepatitis C virus immunogenic compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12296005-B2
Application number	US-202117511177-A
Country	US
Kind code	B2
Filing date	Oct 26, 2021
Priority date	Sep 21, 2016
Publication date	May 13, 2025
Grant date	May 13, 2025

Abstract

The present disclosure provides an immunogenic composition comprising: a) a hepatitis C virus (HCV) heterodimeric polypeptide that includes HCV E1 and E2 polypeptides; b) a T-cell epitope polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2; and c) a pharmaceutically acceptable excipient. The present disclosure provides a method of inducing an immune response, in an individual, to an HCV polypeptide. The present disclosure provides an immunogenic composition comprising: a) a polypeptide that comprises one or more T-cell epitopes present in an HCV protein other than E1 and E2; and b) a pharmaceutically acceptable excipient.

First claim

What is claimed is:

1. An immunogenic composition comprising as separate entities:
a) one or more nucleic acids comprising nucleotide sequences encoding a hepatitis C virus (HCV) E1/E2 heterodimeric polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) an HCV E2 polypeptide;

b) a nucleic acid comprising a nucleotide sequence encoding 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 comprises an amino acid sequence having at least 20% amino acid sequence identity to the amino acid sequence of one of:
a) a TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94, wherein the T-cell epitope polypeptide has a length of 25 amino acids to 35 amino acids;
b) a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99;
c) a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95;
d) a TP70 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:96;
e) a TP100 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:97
f) a TP171 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:89;
g) a TP228 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:81;
h) a TP553 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 100;
i) a TP778 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 101; and
j) a TP1985 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 102; and

c) a pharmaceutically acceptable carrier.

2. The immunogenic composition of claim 1 , wherein:
a) the HCV E2 polypeptide is derived from an HCV of major genotype 1, 2, 3, 4, 5, 6, or 7; and
b) the HCV E1 polypeptide is derived from an HCV of major genotype 1, 2, 3, 4, 5, 6, or 7.

3. The immunogenic composition of claim 1 , wherein the T-cell epitope polypeptide comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of one of:
a) a TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94, wherein the T-cell epitope polypeptide has a length of 25 amino acids to 35 amino acids;
b) a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99;
c) a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95;
d) a TP70 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:96;
e) a TP100 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:97
f) a TP171 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:89;
g) a TP228 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:81;
h) a TP553 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:100;
i) a TP778 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 101; and
j) a TP1985 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:102.

4. The immunogenic composition of claim 1 , comprising an adjuvant.

5. The immunogenic composition of claim 4 , wherein the adjuvant comprises MF59; alum; poly(DL-lactide co-glycolide); a CpG oligonucleotide; keyhole limpet hemocyanin; or a suspension of liposomes comprising 3′-O-desacyl-4′-monophosphoryl lipid A (MPL) and Quillaja saponaria 21 (QS21); AS01; or a mixture of alum and MPL.

6. The immunogenic composition of claim 1 , wherein the one or more nucleic acids are DNA.

7. The immunogenic composition of claim 1 , wherein the one or more nucleic acids are RNA.

8. The immunogenic composition of claim 1 , wherein the one or more nucleic acids are present in one or more recombinant viral expression vectors.

9. The immunogenic composition of claim 8 , wherein the recombinant viral expression vector is a recombinant adenovirus.

10. The immunogenic composition of claim 8 , wherein the recombinant viral expression vector is a recombinant vaccinia virus.

11. A method of inducing an immune response in an individual to a hepatitis C virus (HCV) polypeptide, 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 administration is via intramuscular administration.

13. The method of claim 11 , wherein said administration is via subcutaneous administration.

14. The method of claim 11 , wherein the individual is at greater risk than the general population of becoming infected with HCV.

15. An immunogenic composition comprising a nucleic acid comprising:
a) a first nucleotide sequence encoding a hepatitis C virus (HCV) HCV E1 polypeptide and an HCV E2 polypeptide;
b) a second nucleotide sequence encoding 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 comprises an amino acid sequence having at least 20% amino acid sequence identity to the amino acid sequence of one of:
a) a TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94, wherein the T-cell epitope polypeptide has a length of 25 amino acids to 35 amino acids;
b) a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99;
c) a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95;
d) a TP70 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:96;
e) a TP100 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:97
f) a TP171 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:89;
g) a TP228 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:81;
h) a TP553 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 100;
i) a TP778 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 101; and
j) a TP1985 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 102; and

c) a pharmaceutically acceptable carrier.

16. The immunogenic composition of claim 15 , wherein:
a) the HCV E2 polypeptide is derived from an HCV of major genotype 1, 2, 3, 4, 5, 6, or 7; and
b) the HCV E1 polypeptide is derived from an HCV of major genotype 1, 2, 3, 4, 5, 6, or 7.

17. The immunogenic composition of claim 15 , wherein the T-cell epitope polypeptide comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence of one of:
a) a TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94, wherein the T-cell epitope polypeptide has a length of 25 amino acids to 35 amino acids;
b) a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99;
c) a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95;
d) a TP70 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:96;
e) a TP100 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:97
f) a TP171 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:89;
g) a TP228 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:81;
h) a TP553 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:100;
i) a TP778 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:101; and
j) a TP1985 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:102.

Assignees

• Univ Alberta

Inventors

• Houghton Michael
• Landi Abdolamir
• Logan Michael
• Law John L
• Hockman Darren
• Chen Chao

Classifications

• C12N2710/24143

  viral genome or elements thereof as genetic vector · CPC title

• C12N2710/24134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2710/10043

  viral genome or elements thereof as genetic vector · CPC title

• C12N2710/10034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• A61K2039/55544

  Bacterial toxins · CPC title