Non-neuroinvasive viruses and uses thereof

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.

1 . A variant herpesvirus or alphaherpes virus particle comprising at least two mutations in a UL37 protein comprising a polypeptide having one of SEQ ID NOs: 22-27, 29-33, and 36 or a polypeptide having at least 90% identify to one of SEQ ID NOs: 22-27, 29-33, and 36, wherein the mutations are at positions selected from the group consisting of Q269, D307, R310, H366, and H370 in SEQ ID NO: 22 or at the corresponding positions in one of SEQ ID NOs: 23-27, 29-33, and 36, wherein said virus particle exhibits reduced neuro-invasiveness relative to a virus particle lacking said mutation, and wherein the ability of the virus particle to replicate in peripheral tissues is retained. 
     
     
         2 . The virus particle of  claim 1 , wherein said virus particle is selected from the group consisting of pseudorabies virus (PRV), varicella-zoster virus (VZV), 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 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The virus particle of  claim 1 , wherein the UL37 protein of said virus has at least 95% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 22-27, 29-33 and 36. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The virus particle of  claim 1 , wherein said two or more mutations is two mutations. 
     
     
         10 . The virus particle of  claim 1 , wherein said two or more mutations is three or more mutations. 
     
     
         11 . The virus particle of  claim 1 , wherein said two or more mutations is four or more mutations. 
     
     
         12 . The virus particle of  claim 1 , wherein said two or more mutations is all five of said mutations. 
     
     
         13 . (canceled) 
     
     
         14 . The virus particle of  claim 1 , wherein said virus is avirulent. 
     
     
         15 . A nucleic acid encoding the virus particle of  claim 1 . 
     
     
         16 . A vector comprising the nucleic acid of  claim 15 . 
     
     
         17 . A pharmaceutical composition comprising the virus particle of  claim 1 , a nucleic acid encoding the virus particle, or a vector comprising the nucleic acid encoding the virus particle 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 of  claim 1 , h nucleic acid encoding the virus particle, or a vector comprising the nucleic acid encoding the virus particle and a pharmaceutically acceptable carrier. 
     
     
         20 . The vaccine 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  claim 17  to a subject under conditions such that said subject generates an immune response to said virus. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 21 , wherein said subject is human. 
     
     
         24 . The method of  claim 21 , wherein said subject is a non-human animal 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . A method of preventing infection by a virus, comprising: administering the composition  claim 17  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 . (canceled) 
     
     
         31 . A method of treating or preventing cancer, comprising: administering the composition of  claim 17  to a subject diagnosed with cancer under conditions such that said cancer is reduced or eliminated. 
     
     
         32 . (canceled)