Hepatitis C virus nucleic acid vaccine
The present invention features nucleic acid constructs that can be used as a HCV nucleic acid vaccine, vaccine component, or in the production of a HCV vaccine. Described constructs include those: (1) encoding for a chimeric HCV polypeptide containing a NS3-4A region based on a first HCV strain and an NS3-NS4A-NS4B-NS5A or an NS3-NS4A-NS4B-NS5A-NS5B region based on a second strain; and (2) a chimpanzee based adenovector encoding an HCV polypeptide.
1. A recombinant adenovector comprising:
a) an expression cassette encoding an HCV polypeptide, wherein said HCV polypeptide comprises HCV NS3-NS4A-NS4B-NS5A; and
b) an adenovirus genome containing an E1 deletion, an E3 deletion, and an optional E4 deletion; provided that said genome encodes:
i) a fiber region with an amino acid sequence having an identity of at least 70% to SEQ ID NO: 3 or of at least 80% to SEQ ID NO: 9;
ii) a hexon region with an amino acid sequence having an identity of at least 95% to either SEQ ID NO: 5 or 11; and
iii) a penton region with an amino acid sequence having an identity of at least 85% to SEQ ID NO: 7,
wherein said expression cassette is located at either the E1 or E3 deletion.
2. A pharmaceutical formulation comprising a therapeutically effective amount of the recombinant adenovector of claim 1 .
3. A method of treatment or prophylaxis of hepatitis C in a patient comprising the step of administering to said patient a therapeutically effective amount of the recombinant adenovector of claim 1 .
4. The recombinant adenovector of claim 1 , wherein said HCV polypeptide comprises HCV NS3-NS4A-NS4B-NS5A-NS5B and produces sufficient activity in vivo to process itself to produce an NS5B protein and said NS5B protein is enzymatically inactive; and
said adenovirus genome contains an E4 deletion and insertion of an Ad5 E4orf6 sequence substantially similar to nucleotides 34601-35482 of SEQ ID NO:13.
5. The recombinant adenovector of claim 1 , wherein said vector is substantially similar to SEQ ID NO:13 or SEQ ID NO:17.
6. The recombinant adenovector of claim 5 , wherein said vector consists of the nucleic acid sequence of SEQ ID NO:13 or SEQ ID NO:17.
7. A recombinant adenovirus particle comprising the recombinant adenovirus genome of claim 1 , wherein said particle is encoded by said recombinant adenovirus genome.
8. A recombinant adenovirus particle comprising the recombinant adenovirus genome of claim 4 , wherein said particle is encoded by said recombinant adenovirus genome.
9. A recombinant adenovirus particle comprising the recombinant adenovirus genome of claim 5 , wherein said particle is encoded by said recombinant adenovirus genome.
10. A recombinant adenovirus particle comprising the recombinant adenovirus genome of claim 6 , wherein said particle is encoded by said recombinant adenovirus genome.
11. A pharmaceutical formulation comprising a therapeutically effective amount of the recombinant adenovector of claim 4 and a pharmaceutically acceptable carrier.
12. A pharmaceutical formulation comprising a therapeutically effective amount of the recombinant adenovector of claim 5 and a pharmaceutically acceptable carrier.
13. A pharmaceutical formulation comprising a therapeutically effective amount of the recombinant adenovector of claim 6 and a pharmaceutically acceptable carrier.
14. A method of treatment or prophylaxis of hepatitis C in a patient comprising the step of administering to said patient a therapeutically active amount of the recombinant adenovector of claim 4 .
15. A method of treatment or prophylaxis of hepatitis C in a patient comprising the step of administering to said patient a therapeutically active amount of the recombinant adenovector of claim 5 .
16. A method of treatment or prophylaxis of hepatitis C in a patient comprising the step of administering to said patient a therapeutically active amount of the recombinant adenovector of claim 6 .
17. The recombinant adenovector of claim 1 , wherein the adenovirus genome encodes:
i) a fiber region with an amino acid sequence having an identity of at least 80% to SEQ ID NO: 3 or of at least 85% to SEQ ID NO: 9;
ii) a hexon region with an amino acid sequence having an identity of at least 95% to either SEQ ID NO: 5 or 11; and
iii) a penton region with an amino acid sequence having an identity of at least 90% to SEQ ID NO: 7.
18. The recombinant adenovector of claim 17 , wherein the adenovirus genome encodes:
i) a fiber region with an amino acid sequence having an identity of at least 95% to SEQ ID NO: 3 or of at least 95% to SEQ ID NO: 9;
ii) a hexon region with an amino acid sequence having an identity of at least 95% to either SEQ ID NO: 5 or 11; and
iii) a penton region with an amino acid sequence having an identity of at least 95% to SEQ ID NO: 7.