Non-neuroinvasive viruses and uses thereof

Patent metadata

Field	Value
Publication number	US-10647964-B2
Application number	US-201615555873-A
Country	US
Kind code	B2
Filing date	Mar 4, 2016
Priority date	Mar 5, 2015
Publication date	May 12, 2020
Grant date	May 12, 2020

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 two mutations in a UL37 protein selected from the group consisting if SEQ ID NO: 34, SEQ ID NO: 35, a sequence having at least 90% sequence identity to SEQ ID NO: 34 and a sequence having at least 90% sequence identity to SEQ ID NO: 35, wherein the mutations are at a position selected from the group consisting of Q403, E452, Q455, Q511, and R515, wherein said virus particle exhibits reduced neuro-invasiveness relative to a virus particle lacking said mutation, and wherein the ability of the virus to replicate in peripheral tissues is retained.

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 the UL37 protein of said virus has at least 95% sequence identify to a sequence selected from the group consisting of SEQ ID NOS: 34-35.

4. The virus particle of claim 1 , wherein said one or more mutations is at least two or more.

5. The virus particle of claim 1 , wherein said one or more mutations is at least three or more.

6. The virus particle of claim 1 , wherein said one or more mutations is at least four or more.

7. The virus particle of claim 1 , wherein said one or more mutations is at least all five of said mutations.

8. The virus particle of claim 6 , wherein said virus is avirulent.

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

10. A vector comprising the nucleic acid of claim 9 .

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

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

13. A method of inducing an immune response against a virus, comprising: administering the composition of claim 11 to a subject under conditions such that said subject generates an immune response to said virus.

14. The method of claim 13 , wherein said subject is human or is a non-human animal.

15. A method of preventing infection by a virus, comprising: administering the composition of claim 11 to a subject under conditions such that said subject generates an immune response to said virus.

16. A method of treating or preventing 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 by inducing an immune response to said virus.

Assignees

• Univ Northwestern
• Univ Nebraska
• Tufts College

Inventors

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

Classifications

• A61K39/25

  Varicella-zoster virus · CPC title

• C12N2710/16634

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

• C12N2710/16743

  viral genome or elements thereof as genetic vector · CPC title

• C12N2710/16621

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• C12N2710/16734

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