Hepatitis c virus immunogenic compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11324818-B2
Application number	US-201716334683-A
Country	US
Kind code	B2
Filing date	Sep 21, 2017
Priority date	Sep 21, 2016
Publication date	May 10, 2022
Grant date	May 10, 2022

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) a hepatitis C virus (HCV) E1/E2 heterodimeric polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) an HCV E2 polypeptide;

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 carrier.

2. The immunogenic composition of claim 1 , wherein the T-cell epitope polypeptide comprises one or more T cell epitopes present in one or more of:
a) an HCV non-structural polypeptide-3 (NS3) polypeptide;
b) an HCV non-structural polypeptide-2 (NS2) polypeptide;
c) an HCV non-structural polypeptide-4A (NS4A) polypeptide;
d) an HCV non-structural polypeptide-4B (NS4B) polypeptide;
e) an HCV non-structural polypeptide-5A (NS5A) polypeptide;
f) an HCV non-structural polypeptide-5B (NS5B) polypeptide;
g) an HCV core polypeptide; and
h) an HCV p7 polypeptide.

3. 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.

4. The immunogenic composition of claim 1 , wherein the T-cell epitope polypeptide has a length of from about 10 amino acids to about 3000 amino acids.

5. The immunogenic composition of claim 1 , wherein the T-cell epitope polypeptide comprises one or more T cell epitopes present in an HCV NS3 polypeptide.

6. The immunogenic composition of claim 5 , 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 TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94, a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99, a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95, a TP70 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:96, a TP100 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:97, a TP171 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:89, a TP228 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:81, a TP553 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:100, a TP778 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:101, and a TP1985 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:102.

7. The immunogenic composition of claim 1 , wherein the T-cell epitope polypeptide comprises one or more T cell epitopes present in:
a) cholera toxin or toxoid; and/or
b) tetanus toxin or toxoid; and/or
c) diphtheria toxin or toxoid; and/or
d) CRM197.

8. The immunogenic composition of claim 1 , wherein the composition comprises a polypeptide comprising one or more T cell epitopes present in:
a) cholera toxin or toxoid; and/or
b) tetanus toxin or toxoid; and/or
c) diphtheria toxin or toxoid; and/or
d) CRM197.

9. The immunogenic composition of claim 1 , wherein the E2 polypeptide and/or the E1 polypeptide lacks a C-terminal transmembrane domain.

10. The immunogenic composition of claim 1 , wherein the HCV E1/E2 heterodimeric polypeptide comprises:
a) an HCV E1 polypeptide; and
b) a modified E2 polypeptide comprising, in order from N-terminus to C-terminus:
i) from 1 to 6 heterologous amino acids, wherein the from 1 to 6 heterologous amino acids are C-terminal to a site of proteolytic cleavage in a proteolytically cleavable linker; and
ii) an HCV E2 polypeptide; or

a) an HCV E2 polypeptide; and
b) a modified E1 polypeptide comprising, in order from N-terminus to C-terminus:
i) from 1 to 6 heterologous amino acids, wherein the from 1 to 6 heterologous amino acids are C-terminal to a site of proteolytic cleavage in a proteolytically cleavable linker; and
ii) an HCV E1 polypeptide; or

a) an HCV E1 polypeptide; and
b) a modified E2 polypeptide comprising, in order from N-terminus to C-terminus:
i) an HCV E2 polypeptide; and
ii) from 1 to 6 heterologous amino acids, wherein the from 1 to 6 heterologous amino acids are N-terminal to a site of proteolytic cleavage in a proteolytically cleavable linker; or

a) an HCV E2 polypeptide; and
b) a modified E1 polypeptide comprising, in order from N-terminus to C-terminus:
i) an HCV E1 polypeptide; and
ii) from 1 to 6 heterologous amino acids, wherein the from 1 to 6 heterologous amino acids are N-terminal to a site of proteolytic cleavage in a proteolytically cleavable linker.

11. The immunogenic composition of claim 10 , wherein:
a) the from 1 to 6 heterologous amino acids at the N-terminus of the modified E2 polypeptide or the modified E1 polypeptide are Gly-Pro, Ser, Gly, or Gly-Ser; or
b) the from 1 to 6 heterologous amino acids at the C-terminus of the modified E2 polypeptide or the modified E1 polypeptide are LEVLFQ as set forth in SEQ ID NO:76, ENLYYFQ as set forth in SEQ ID NO:83, LVPR as set forth in SEQ ID NO:78, I(E/D)GR as set forth in SEQ ID NO:90, or DDDDK as set forth in SEQ ID NO:77.

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

13. The immunogenic composition of claim 12 , 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.

14. A method of inducing an immune response in an individual to a hepatitis C virus (HCV) polypeptide, the method comprising administering to the individual:
a) an effective amount of the immunogenic composition of claim 1 ; or
b) one or more nucleic acids comprising nucleotide sequences encoding the HCV E1/E2 heterodimeric polypeptide and the T-cell epitope polypeptide of claim 1 .

15. An immunogenic composition comprising:
a1) a hepatitis C virus (HCV) heterodimeric polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) a modified HCV E2 polypeptide comprising a heterologous Gly-Pro, Gly-Ser, Gly, or Ser appended to the N-terminus of an HCV E2 polypeptide;

b1) a T-cell epitope polypeptide comprising an amino acid sequence having at least 95% amino acid sequence identity to a TP29 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:94 and having a length of 29 amino acids; and
c1) a pharmaceutically acceptable carrier; or
a2) a hepatitis C virus (HCV) heterodimeric polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) a modified HCV E2 polypeptide comprising a heterologous Gly-Pro, Gly-Ser, Gly, or Ser appended to the N-terminus of an HCV E2 polypeptide;

b2) a T-cell epitope polypeptide comprising an amino acid sequence having at least 95% amino acid sequence identity to a TP50 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:99 and having a length of 50 amino acids; and
c2) a pharmaceutically acceptable carrier; or
a3) a hepatitis C virus (HCV) heterodimeric polypeptide comprising:
i) an HCV E1 polypeptide; and
ii) a modified HCV E2 polypeptide comprising a heterologous Gly-Pro, Gly-Ser, Gly, or Ser appended to the N-terminus of an HCV E2 polypeptide;

b3) a T-cell epitope polypeptide comprising an amino acid sequence having at least 95% amino acid sequence identity to a TP52 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:95 and having a length of 52 amino acids; and
c3) a pharmaceutically acceptable carrier; or
a4) a hepatitis C virus (HCV) heterodimeric polypeptide comprising:

Assignees

• Univ Alberta

Inventors

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

Classifications

• A61K2039/55544

  Bacterial toxins · CPC title

• C12N2710/10034

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

• A61K39/12

  Viral antigens · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• C12N2770/24234

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