Non-Neuroinvasive Viruses and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2020263147-A1
Application number	US-202016868246-A
Country	US
Kind code	A1
Filing date	May 6, 2020
Priority date	Mar 5, 2015
Publication date	Aug 20, 2020
Grant date	—

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 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), herpes simplex virus-2 (HSV-2), pseudorabies virus (PRV), varicella-zoster virus (VRV), bovine herpesvirus-1 (BHV-1), bovine herpes virus 5 (BHV-5); equine herpes virus 1 (EHV-1); equine herpes virus 3 (EHV-3); and equine herpes virus 4 (EHV-4).

3 . The virus particle of claim 1 or 2 , wherein said the UL37 protein of said virus has at least 70% sequence identify to a sequence selected from the group consisting of SEQ ID NOS: 22-36.

4 . The virus particle of claim 1 or 2 , wherein said the UL37 protein of said virus has at least 90% sequence identify to a sequence selected from the group consisting of SEQ ID NOS: 22-36.

5 . The virus particle of claim 1 or 2 , 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: 22-36.

6 . A variant HSV 1 or 2 particle comprising a mutant UL37 protein, wherein said mutant UL37 protein comprises one or more mutations selected from the group consisting of Q403A, E452A, Q455A, Q511A, and R515A.

7 . A variant VZV virus particle comprising a mutant UL37 protein, wherein said mutant UL37 protein comprises one or more mutations selected from the group consisting of Q363A, D413A, Q416A, Q472A, and R476A.

8 . A variant PRV particle comprising a mutant UL37 protein, wherein said mutant UL37 protein comprises one or more mutations selected from the group consisting of Q324A, D362A, R365A, H421A, and H425A.

9 . The virus particle of any one of claims 1 to 8 , wherein said one or more mutations is two or more.

10 . The virus particle of any one of claims 1 to 8 , wherein said one or more mutations is three or more.

11 . The virus particle of any one of claims 1 to 8 , wherein said one or more mutations is four or more.

12 . The virus particle of any one of claims 1 to 8 , wherein said one or more mutations is all of said mutations.

13 . The virus particle of any one of claims 1 to 12 , wherein said virus particle exhibits reduced neuro-invasiveness relative to a virus particle lacking said mutations.

14 . The virus particle of any one of claims 1 to 13 , wherein said virus is avirulent.

15 . A nucleic acid encoding the virus particle of any one of claims 1 to 14 .

16 . A vector comprising the nucleic acid of claim 15 .

17 . A pharmaceutical composition comprising the virus particle, nucleic acid, or vector of any one of claims 1 to 16 and a pharmaceutically acceptable carrier.

18 . The pharmaceutical composition of claim 17 , wherein said composition further comprises an adjuvant.

19 . A vaccine composition comprising the virus particle, nucleic acid, or vector of any one of claims 1 to 16 and a pharmaceutically acceptable carrier.

20 . The vaccine composition of claim 19 , wherein said composition further comprises an adjuvant.

21 . A method of inducing an immune response against a virus, comprising:
administering the composition of any one of claims 17 to 20 to a subject under conditions such that said subject generates an immune response to said virus.

22 . The method of claim 21 , wherein said subject exhibits immunity to said virus.

23 . The method of claim 21 or 22 , wherein said subject is human.

24 . The method of claim 21 or 22 , wherein said subject is a non-human animal.

25 . The use of the composition of any one of claims 17 to 20 to generate an immune response against a virus in a subject.

26 . The use of claim 25 , wherein said subject exhibits immunity against said virus.

27 . The use of claim 25 or 26 , wherein said subject is human.

28 . The use of claim 25 or 26 , wherein said subject is a non-human animal.

29 . A method of preventing infection by a virus, comprising:
administering the composition of any one of claims 17 to 20 to a subject under conditions such that said subject generates an immune response to said virus and is immune to infection by said virus.

30 . The use of the composition of any one of claims 17 to 20 to prevent infection by a virus in a subject.

31 . A method of treating or preventing cancer, comprising:
administering the composition of any one of claims 17 to 20 to a subject diagnosed with cancer under conditions such that said cancer is reduced or eliminated.

32 . The use of the composition of any one of claims 17 to 20 to treat cancer in a subject diagnosed with cancer.

Assignees

• Univ Northwestern
• Univ Nebraska
• Trustees Of Tufts College (Aka Tufts University)

Inventors

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

Classifications

• A61K39/12 Primary

  Viral antigens · CPC title

• C12N2710/16732

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title

• C12N2710/16632

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title

• C12N2710/16722

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

• C12N2710/16622

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