Non-neuroinvasive viruses and uses thereof

Patent metadata

Field	Value
Publication number	US-11339378-B2
Application number	US-202016868246-A
Country	US
Kind code	B2
Filing date	May 6, 2020
Priority date	Mar 5, 2015
Publication date	May 24, 2022
Grant date	May 24, 2022

Abstract

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

First claim

We claim:

1. A variant herpesvirus or alphaherpes virus particle comprising at least one mutation in a UL37 protein, wherein said UL37 protein has at least 90% sequence identity to SEQ ID NO: 34 or SEQ ID NO: 35, wherein said at least one mutation is at one or more amino acid positions selected from the group consisting of Q403, E452, Q455, Q511, and R515, and wherein said virus particle exhibits reduced neuro-invasiveness relative to a virus particle lacking said mutation.

2. The virus particle of claim 1 , wherein said virus is selected from the group consisting of herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2).

3. The virus particle of claim 1 , wherein said UL37 protein of said virus has at least 95% sequence identity to a sequence according to SEQ ID NO: 34 or SEQ ID NO: 35.

4. The virus particle of claim 1 , wherein the ability of said virus to replicate in peripheral tissues is retained.

5. The virus particle of claim 1 , wherein said at least one mutation is selected from Q403A, E452A, Q455A, Q511A, and R515A.

6. The virus particle of claim 1 , wherein said at least one mutation is at two or more of said amino acid positions.

7. The virus particle of claim 1 , wherein said at least one mutation is at three or more of said amino acid positions.

8. The virus particle of claim 1 , wherein said at least one mutation is at four or more of said amino acid positions.

9. The virus particle of claim 1 , wherein said at least one mutation is at all five of said amino acid positions.

10. The virus particle of claim 7 , wherein said at least one mutation comprises Q403A, E452A, Q455A, Q511A, and R515A.

11. The virus particle of claim 1 , wherein said virus is avirulent.

12. A nucleic acid encoding the virus particle of claim 1 .

13. A vector comprising the nucleic acid of claim 12 .

14. A pharmaceutical composition comprising the virus particle of claim 1 , a nucleic acid encoding the virus particle of claim 1 , or a vector comprising the nucleic acid encoding the virus particle of claim 1 and a pharmaceutically acceptable carrier.

15. A vaccine composition comprising the virus particle of claim 1 , a nucleic acid encoding the virus particle of claim 1 , or a vector comprising the nucleic acid encoding the virus particle of claim 1 and a pharmaceutically acceptable carrier.

16. A method of inducing an immune response against a virus, comprising:
administering the composition of claim 14 to a subject under conditions such that said subject generates an immune response to said virus.

17. The method of claim 16 , wherein said subject is human or is a non-human animal.

18. A method of preventing infection by a virus, comprising:
administering the composition of claim 14 to a subject under conditions such that said subject generates an immune response to said virus.

19. A method of treating cancer, comprising:
administering the composition of claim 11 to a subject diagnosed with cancer under conditions such that the growth of said cancer is reduced.

20. The method of claim 19 , wherein the composition is administered intravenously.

21. The method of claim 19 , wherein the composition is administered in combination with an anti-cancer agent.

22. The method of claim 21 , wherein said anti-cancer agent comprises an alkaloid, a covalent DNA-binding agent (alkylating agent), a noncovalent DNA-binding agent, an antimetabolite, an agent that induces tumor cell differentiation, or a platinum compound.

23. The method of claim 21 , wherein said anti-cancer agent comprises an enzyme, a hormone, an antisense therapy technique, a hematopoietic growth factor, or an angiogenesis inhibitor.

24. The method of claim 21 , wherein said anti-cancer agent comprises a proteosome inhibitor, an inhibitor of acetylation and/or methylation, a NF kappa B modulator, an inhibitor of cell cycle regulation, or a modulator of p53 protein function.

25. The method of claim 21 , wherein said anti-cancer agent comprises an interferon, an interleukin, a tumor vaccine, or a monoclonal antibody conjugated with an anticancer drug, toxin, and/or radionuclide.

26. The method of claim 19 , used in combination with radiation or adoptive immunotherapy.

Assignees

• Univ Northwestern
• Univ Nebraska
• Tufts College

Inventors

• Smith Gregory A
• Sollars Patricia Jane
• Pickard Gary Edward
• Heldwein Ekaterina E

Classifications

• A61K39/12 Primary

  Viral antigens · CPC title

• C12N2710/16034

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

• A61K2039/5254

  avirulent or attenuated · CPC title

• C12N2710/16634

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

• C12N2710/16722

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title