Hepatitis C virus immunogenic compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12005116-B2
Application number	US-202318099044-A
Country	US
Kind code	B2
Filing date	Jan 19, 2023
Priority date	Jul 7, 2015
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

The present disclosure provides heterodimeric polypeptides comprising: 1) a variant hepatitis C virus (HCV) E2 polypeptide and an HCV E1 polypeptide; 2) a variant HCV E1 polypeptide and an HCV E2 polypeptide; or 3) a variant HCV E1 polypeptide and a variant HCV E2 polypeptide, where the variant HCV E2 polypeptide and/or the HCV E1 polypeptide comprises one or more T cell epitopes, present in an HCV polypeptide other than an HCV E1 polypeptide or an HCV E2 polypeptide. The present disclosure provides nucleic acids encoding a polyprotein that includes E1 and variant E2, E2 and variant E1, or variant E2 and variant E1. The present disclosure provides a method of producing an E1/E2 heterodimer of the present disclosure. The present disclosure provides a method of inducing an immune response in an individual. The present disclosure provides variant E2 polypeptides and variant E1 polypeptides; and nucleic acids encoding same.

First claim

What is claimed is:

1. A heterodimeric polypeptide comprising:
a) a variant hepatitis C virus (HCV) E2 polypeptide comprising:
i) an HCV E2 polypeptide; and
ii) a heterologous polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2,

wherein the heterologous polypeptide:
i) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP29 amino acid sequence set forth in SEQ ID NO:1, wherein the heterologous polypeptide has a length of from 29 amino acids to 32 amino acids;
ii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP50 amino acid sequence set forth in SEQ ID NO:11, wherein the heterologous polypeptide has a length of from 50 amino acids to 55 amino acids;
iii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP52 amino acid sequence set forth in SEQ ID NO:2, wherein the heterologous polypeptide has a length of from 52 amino acids to 55 amino acids;
iv) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP70 amino acid sequence set forth in SEQ ID NO:3, wherein the heterologous polypeptide has a length of from 70 amino acids to 75 amino acids;
v) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP100 amino acid sequence set forth in SEQ ID NO:4, wherein the heterologous polypeptide has a length of from 100 amino acids to 105 amino acids;
vi) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP171 amino acid sequence set forth in SEQ ID NO:63, wherein the heterologous polypeptide has a length of from 171 amino acids to 175 amino acids;
vii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP228 amino acid sequence set forth in SEQ ID NO:10, wherein the heterologous polypeptide has a length of from 228 amino acids to 232 amino acids;
viii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP553 amino acid sequence set forth in SEQ ID NO:12, wherein the heterologous polypeptide has a length of from 553 amino acids to 560 amino acids;
ix) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP778 amino acid sequence set forth in SEQ ID NO:64, wherein the heterologous polypeptide has a length of about 778 amino acids; or
x) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP1985 amino acid sequence set forth in SEQ ID NO:13, wherein the heterologous polypeptide has a length of about 1985 amino acids; and
b) an HCV E1 polypeptide.

2. The heterodimeric polypeptide of claim 1 , wherein:
a) the HCV E2 polypeptide is derived from an HCV of genotype 1, 2, 3, or 7; and
b) the HCV E1 polypeptide is derived from an HCV of genotype 1, 2, 3, or 7.

3. The heterodimeric polypeptide of claim 1 , wherein the HCV E2 polypeptide comprises an amino acid sequence having at least 20% amino acid sequence identity to an E2 polypeptide depicted in one of FIGS. 1 A- 1 C , FIGS. 2 A- 2 C , FIGS. 3 A- 3 C , and FIGS. 4 A- 4 B .

4. The heterodimeric polypeptide of claim 1 , wherein the HCV E2 polypeptide comprises an amino acid sequence having at least 50% amino acid sequence identity to an E2 polypeptide depicted in one of FIGS. 1 A- 1 C , FIGS. 2 A- 2 C , FIGS. 3 A- 3 C , and FIGS. 4 A- 4 B .

5. The heterodimeric polypeptide of claim 1 , wherein the HCV E1 polypeptide comprises an amino acid sequence having at least 20% amino acid sequence identity to an E1 polypeptide depicted in FIGS. 1 A- 1 C , FIGS. 2 A- 2 C , FIGS. 3 A- 3 C , and FIGS. 4 A- 4 B .

6. The heterodimeric polypeptide of claim 1 , wherein the HCV E1 polypeptide comprises an amino acid sequence having at least 50% amino acid sequence identity to an E1 polypeptide depicted in FIGS. 1 A- 1 C , FIGS. 2 A- 2 C , FIGS. 3 A- 3 C , and FIGS. 4 A- 4 B .

7. The heterodimeric polypeptide of claim 1 , wherein the modified HCV E2 polypeptide and the HCV E1 polypeptide are derived from an HCV of the same genotype.

8. The heterodimeric polypeptide of claim 1 , wherein the modified HCV E2 polypeptide and the HCV E1 polypeptide are derived from an HCV of different genotypes.

9. A heterodimeric polypeptide comprising:
a) a variant hepatitis C virus (HCV) E1 polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) a heterologous polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2,

wherein the heterologous polypeptide:
i) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP29 amino acid sequence set forth in SEQ ID NO:1, wherein the heterologous polypeptide has a length of from 29 amino acids to 32 amino acids;
ii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP50 amino acid sequence set forth in SEQ ID NO:11, wherein the heterologous polypeptide has a length of from 50 amino acids to 55 amino acids;
iii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP52 amino acid sequence set forth in SEQ ID NO:2, wherein the heterologous polypeptide has a length of from 52 amino acids to 55 amino acids;
iv) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP70 amino acid sequence set forth in SEQ ID NO:3, wherein the heterologous polypeptide has a length of from 70 amino acids to 75 amino acids;
v) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP100 amino acid sequence set forth in SEQ ID NO:4, wherein the heterologous polypeptide has a length of from 100 amino acids to 105 amino acids;
vi) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP171 amino acid sequence set forth in SEQ ID NO:63, wherein the heterologous polypeptide has a length of from 171 amino acids to 175 amino acids;
vii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP228 amino acid sequence set forth in SEQ ID NO:10, wherein the heterologous polypeptide has a length of from 228 amino acids to 232 amino acids;
viii) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP553 amino acid sequence set forth in SEQ ID NO:12, wherein the heterologous polypeptide has a length of from 553 amino acids to 560 amino acids;
ix) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP778 amino acid sequence set forth in SEQ ID NO:64, wherein the heterologous polypeptide has a length of about 778 amino acids; or
x) comprises an amino acid sequence having at least 20% amino acid sequence identity to the TP1985 amino acid sequence set forth in SEQ ID NO:13, wherein the heterologous polypeptide has a length of about 1985 amino acids; and
b) an HCV E2 polypeptide.

10. The heterodimeric polypeptide of claim 9 , wherein:
a) the HCV E2 polypeptide is derived from an HCV of genotype 1, 2, 3, or 7; and
b) the HCV E1 polypeptide is derived from an HCV of genotype 1, 2, 3, or 7.

11. The heterodimeric polypeptide of claim 9 , wherein the HCV E2 polypeptide comprises an amino acid sequence having at least 20% amino acid sequence identity to an E2 polypeptide depicted in one of FIGS. 1 A- 1 C , FIGS. 2 A- 2 C , FIGS. 3 A- 3 C , and FIGS. 4 A- 4 B .

12. The heterodimeric polypeptide of claim 9 , wherein the HCV E2 polypeptide comprises an amino acid sequence having at least 50% amino acid sequence identity to an E2 polypeptide depicted in one of FIGS

Assignees

• Univ Alberta

Inventors

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

Classifications

• C12N15/861

  Adenoviral vectors · CPC title

• A61K2039/55544

  Bacterial toxins · CPC title

• A61K39/295

  Polyvalent viral antigens (vaccinia virus or variola virus A61K39/285); Mixtures of viral and bacterial antigens · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/14

  for RNA viruses · CPC title