Human cytomegalovirus comprising exogenous antigens

Patent metadata

Field	Value
Publication number	US-11692012-B2
Application number	US-202117214598-A
Country	US
Kind code	B2
Filing date	Mar 26, 2021
Priority date	Jul 16, 2014
Publication date	Jul 4, 2023
Grant date	Jul 4, 2023

Abstract

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

First claim

The invention claimed is:

1. A recombinant human cytomegalovirus (HCMV) comprising:
(1) a first nucleic acid encoding at least one heterologous antigen;
(2) an inactivating mutation in the UL45 gene; and
(3) active US2, US3, US6, US7, UL97, and UL131A genes;
wherein the recombinant HCMV is a genetically modified TR strain of HCMV; and the recombinant HCMV is ganciclovir-sensitive.

2. The recombinant HCMV of claim 1 , wherein the US2, US3, US6, US7, and UL97 genes are derived from the AD169 strain of HCMV.

3. The recombinant HCMV of claim 1 , wherein expression of the first nucleic acid encoding at least one heterologous antigen is driven by the UL82 promoter, the UL7 promoter, the UL45 promoter, the UL78 promoter, or the US13 promoter.

4. The recombinant HCMV of claim 1 , wherein the inactivating mutation in the UL45 gene is a deletion of all or part of the UL45 gene.

5. The recombinant HCMV of claim 4 , wherein the first nucleic acid encoding at least one heterologous antigen replaces all or part of the UL45 gene.

6. The recombinant HCMV of claim 5 , wherein expression of the first nucleic acid encoding at least one heterologous antigen replacing all or part of the UL45 gene is driven by the UL45 gene promoter.

7. The recombinant HCMV of claim 1 , further comprising an inactivating mutation in a HCMV UL7 gene or UL38 gene.

8. The recombinant HCMV of claim 7 , wherein the inactivating mutation in the UL7 gene is a deletion of all or part of the UL7 gene.

9. The recombinant HCMV of claim 8 , wherein the first nucleic acid encoding at least one heterologous antigen replaces all or part of the UL7 gene.

10. The recombinant HCMV of claim 9 , wherein expression of the first nucleic acid encoding at least one heterologous antigen replacing all or part of the UL7 gene is driven by the UL7 promoter.

11. The recombinant HCMV of claim 7 , wherein the inactivating mutation in the UL38 gene is a deletion of all or part of the UL38 gene.

12. The recombinant HCMV of claim 11 , wherein the first nucleic acid encoding at least one heterologous antigen replaces all or part of the UL38 gene.

13. The recombinant HCMV of claim 12 , wherein expression of the first nucleic acid encoding at least one heterologous antigen replacing all or part of the UL38 gene is driven by the UL38 promoter.

14. The recombinant HCMV of claim 1 , further comprising an inactivating mutation in the UL128 gene or the UL130 gene.

15. The recombinant HCMV of claim 14 , wherein the recombinant HCMV comprises an inactivating mutation in the UL128 gene and the UL130 gene.

16. The recombinant HCMV of claim 1 , wherein the at least one heterologous antigen is a pathogen specific antigen or tumor antigen.

17. The recombinant HCMV of claim 1 , further comprising a second nucleic acid encoding a second heterologous antigen.

18. The recombinant HCMV of claim 17 , wherein the first nucleic acid encoding the first heterologous antigen replaces all or part of the UL45 gene, and wherein the second nucleic acid encoding the second heterologous antigen replaces all or part of the UL7 gene.

19. The recombinant HCMV of claim 18 , wherein the expression of the first nucleic acid encoding the first heterologous antigen is driven by the UL45 promoter, and wherein the expression of the second nucleic acid encoding the second heterologous antigen is driven by the UL7 promoter.

20. The recombinant HCMV of claim 17 , wherein the first nucleic acid encoding the first heterologous antigen replaces all or part of the UL45 gene, and wherein the second nucleic acid encoding the second heterologous antigen replaces all or part of the US13 gene.

21. The recombinant HCMV of claim 20 , wherein the expression of the first nucleic acid encoding the first heterologous antigen is driven by the UL45 promoter, and wherein the expression of the second nucleic acid encoding the second heterologous antigen is driven by the US13 promoter.

22. The recombinant HCMV of claim 17 , wherein the first heterologous antigen is a pathogen specific antigen or tumor antigen.

23. The recombinant HCMV of claim 22 , wherein the second heterologous antigen is a pathogen specific or tumor antigen that is different from the first heterologous antigen.

24. An immunogenic composition comprising the recombinant HCMV of claim 1 and a pharmaceutically acceptable carrier.

25. An immunogenic composition comprising the recombinant HCMV of claim 17 and a pharmaceutically acceptable carrier.

26. An isolated polynucleotide that encodes the recombinant HCMV of claim 1 .

27. An isolated cell comprising the polynucleotide of claim 26 .

28. The isolated cell of claim 27 , wherein the isolated cell is a mammalian cell.

29. The isolated cell of claim 28 , wherein the isolated cell is a human cell.

30. The isolated cell of claim 27 , wherein the isolated cell is a fibroblast.

Assignees

• Univ Oregon Health & Science

Inventors

• Frueh Klaus
• Hansen Scott G
• Nelson Jay
• Picker Louis
• Caposio Patrizia

Classifications

• A61K39/0011

  Cancer antigens · CPC title

• C12N2740/15034

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

• C12N15/85

  for animal cells · CPC title

• C12N2710/16143

  viral genome or elements thereof as genetic vector · CPC title

• A61K39/12 Primary

  Viral antigens · CPC title