Recombinant virus with diminished latency and methods of using same

Patent metadata

Field	Value
Publication number	US-2022193227-A1
Application number	US-202217692540-A
Country	US
Kind code	A1
Filing date	Mar 11, 2022
Priority date	Nov 9, 2006
Publication date	Jun 23, 2022
Grant date	—

Abstract

The disclosure provides recombinant herpes virus with diminished latency. In embodiments, the recombinant herpes virus comprises a latency gene or transcript linked to an altered or heterologous promoter. The disclosure also provides compositions and methods for inducing immunity in animals using the recombinant herpes viruses.

First claim

1 . A method for making an attenuated live virus having an impaired ability to establish latency, comprising:
introducing a recombinant virus comprising all or a portion of a herpes virus genome into a host cell to produce an amount of the recombinant virus suitable for a vaccine, wherein the recombinant virus genome comprises a promoter for a latency gene or transcript that is altered or modified, and the gene or transcript is expressed from the recombinant virus genome during viral replication; and recovering the recombinant virus from the host cell.

2 . The method of claim 1 , wherein the herpes virus is selected from the group consisting of herpes simplex virus, varicella-zoster virus (VZV), Marek's disease virus, pseudorabies virus and cytomegalovirus.

3 . The method of claim 1 , wherein the promoter for the latency gene or transcript is replaced by a heterologous promoter.

4 . The method of claim 1 , wherein the recombinant virus genome comprises a deletion in a latency gene or transcript at its native location, and the latency gene or transcript is located at a different location in the viral genome and is expressed from a heterologous promoter.

5 . The method of claim 1 , wherein the latency gene is a VZV gene selected from the group consisting of ORF4, ORF21, ORF29, ORF62, ORF63 and ORF66.

6 . The method of claim 5 , wherein the latency gene is the VZV ORF29 gene and encodes a major DNA binding protein.

7 . The method of claim 1 , wherein the recombinant virus substantially lacks a DNA binding protein encoding gene at its native location, the gene being encoded by a nucleic acid sequence that hybridizes to a nucleic acid sequence that encodes a ORF29 protein of VZV.

8 . The method of claim 7 , wherein the nucleic acid encoding the major DNA binding protein has a deletion of a nucleic acid that encodes at least 10 amino acids.

9 . The method of claim 8 , wherein amino acids corresponding to amino acids 22-957 of an ORF29 having the amino acid sequence of SEQ ID NO: 3 are deleted.

10 . A method for making an attenuated live virus having an impaired ability to establish latency, comprising:
introducing a recombinant virus comprising all or a portion of a herpes virus genome into a host cell to produce an amount of the recombinant virus suitable for a vaccine, wherein the recombinant virus genome comprises a latency gene or transcript and the latency gene or transcript is at a different location in the genome relative to its native location; and recovering the recombinant virus from the host cell.

11 . The method of claim 10 , wherein the latency gene or transcript comprises at least one mutation.

12 . The method of claim 11 , wherein the latency gene is VZV ORF29 and the mutation is a deletion or substitution in the nuclear localization sequence that impairs the ability of ORF29 to translocate to the nucleus.

13 . The method of claim 10 , wherein the latency gene is located in a position corresponding to that between ORF65 and ORF66 of VZV.

Assignees

• Us Health

Inventors

• Cohen Jeffrey I
• Pesnicak Lesley

Classifications

• C07K14/005

  from viruses · CPC title

• C12N2710/16761

  Methods of inactivation or attenuation · CPC title

• C12N2710/16722

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

• A61K2039/5254

  avirulent or attenuated · CPC title

• C12N15/86

  Viral vectors · CPC title