IP Library Granted Patent US 9,453,239
Granted Patent B2
US 9,453,239 · App. 11/574,285 · Granted Sep 27, 2016

Recombinant MVA viruses expressing clade A/G, clade B, and clade C modified HIV env, gag and pol genes

Inventors: Bernard Moss (Bethesda, MD); Linda Wyatt (Rockville, MD); Harriet L. Robinson (Atlanta, GA)
Assignees: Emory University; The Government of the United States of America, as represented by the Secretary Department of Health and Human Services, National Institutes of Health
C12N15/86C07K14/005A61K2039/5256A61K2039/53A61K2039/57C12N2710/24143C12N2740/16023C12N2740/16122C12N2740/16134C12N2740/16222C12N2740/16234C12N2830/00C12N2830/15C12N2830/60
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Quick Facts
Patent No.
US 9,453,239
App. No.
11/574,285
Granted
Sep 27, 2016
Kind
B2
Abstract

The invention provides modified vaccinia Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing human immunodeficiency virus (HIV) env, gag, and pol genes.

Claims (24)

1. A pharmaceutical composition comprising a recombinant MVA virus comprising a sequence encoding an HIV Env antigen inserted into deletion site II of an MVA and a sequence encoding HIV Gag and Pol antigens inserted into deletion site III of the MVA genome, and a pharmaceutically acceptable carrier;

wherein the sequence encoding the HIV Env antigen comprises SEQ ID NO:3 and the sequence encoding the HIV Gag and Pol antigens comprises SEQ ID NO: 4;

wherein the transcription of the sequence encoding the HIV Env antigen is under the control of a first promoter and transcription of the sequence encoding the HIV Gag and Pol antigens is under the control of a second promoter and wherein the noncoding sequence between the first promoter and the initiation codon of the sequence encoding the HIV Env antigen comprises SEQ ID NO:8.

2. A recombinant MVA virus comprising a sequence encoding an HIV Env antigen inserted into deletion site II of an MVA and a sequence encoding HIV Gag and Pol antigens inserted into deletion site III of the MVA;

wherein the sequence encoding the HIV Env antigen consists of SEQ ID NO:3 and the sequence encoding the HIV Gag and Pol antigens comprises SEQ ID NO: 4;

wherein the transcription of the sequence encoding the HIV Env antigen is under the control of a first promoter and transcription of the sequence encoding the HIV Gag and Pol antigens is under the control of a second promoter and wherein the non-coding sequence between the first promoter and the initiation codon of the sequence encoding the HIV Env antigen comprises SEQ ID NO:8.

3. A recombinant MVA virus comprising a sequence encoding an HIV Env antigen inserted into deletion site II of the MVA and a sequence encoding HIV Gag and Pol antigens inserted into deletion site III of the MVA;

wherein the sequence encoding the HIV Env antigen comprises SEQ ID NO:3 and the sequence encoding the HIV Gag and Pol antigens comprises SEQ ID NO: 4;

wherein the transcription of the sequence encoding the HIV Env antigen is under the control of a first promoter and transcription of the sequence encoding the HIV Gag and Pol antigens is under the control of a second promoter and wherein the sequence between the first promoter and the initiation codon of the sequence encoding the HIV Env antigen comprises SEQ ID NO:8.

4. A recombinant MVA virus comprising a sequence encoding an HIV Env antigen inserted into deletion site II of the MVA and a sequence encoding HIV Gag and Pol antigens inserted into deletion site III of the MVA;

wherein the sequence encoding the HIV Env antigen consists of SEQ ID NO:3 and the sequence encoding the HIV Gag and Pol antigens consists of SEQ ID NO: 4;

wherein the transcription of the sequence encoding the HIV Env antigen is under the control of a first promoter and transcription of the sequence encoding the HIV Gag and Pol antigens is under the control of a second promoter and wherein the sequence between the first promoter and the initiation codon of the sequence encoding the HIV Env antigen comprises SEQ ID NO:8.

5. The pharmaceutical composition of claim 1 wherein the composition is formulated for intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal, intradermal, or mucosal routes.

6. The pharmaceutical composition of claim 1 wherein the composition further comprises at least one pharmaceutically acceptable excipient, carrier, buffer, and/or stabilizer.

7. The pharmaceutical composition of claim 6 wherein the composition further comprises physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol.

8. The recombinant MVA virus of any of claims 1 , 2 and 3 - 4 constructed from MVA 1974/NIH Clone 1.

9. The recombinant MVA virus of any of claims 1 , 2 and 3 - 4 wherein both the first promoter and the second promoter comprise the mH5 promoter.

10. A method of boosting a CD8 + T cell or antibody immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising administering to the primate the composition of any of claims 1 , 2 and 3 - 4 , whereby a CD8 + T cell or antibody immune response to the antigen previously primed in the primate by previous administration of a nucleic acid molecule encoding a Env, Gag, or Pol antigen is boosted.

11. A method of inducing a CD8 + T cell or antibody immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising administering to the primate a priming composition comprising a nucleic acid molecule encoding an HIV Env, Gag, or Pol antigen and then administering to the primate the recombinant MVA of any of claims 1 , 2 and 3 - 4 , whereby a CD8 + T cell or antibody immune response to the antigen is induced.

12. The method of claim 10 , wherein the primate is a human.

13. The recombinant MVA virus of claim 8 wherein both the first promoter and the second promoter comprise the mH5 promoter.

14. The method of claim 11 , wherein the primate is a human.

15. The method of claim 10 , wherein the recombinant MVA is administered at a dose of about 10 6 to 10 9 infectious virus particles/injection.

16. The method of claim 11 , wherein the recombinant MVA is administered at a dose of about 10 6 to 10 9 infectious virus particles/injection.

Assignments (3)
EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded Jul 18, 2008
From: EMORY UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 021261/0752 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 29, 2007
From: MOSS, BERNARD; WYATT, LINDA S.
To: THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTE OF HEALTH
Reel/Frame 019085/0517 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 29, 2007
From: ROBINSON, HARRIET L.
To: EMORY UNIVERSITY
Reel/Frame 019085/0570 →
Continuity (2)
Provisional Application 60604918 · Aug 27, 2004
Related Publication 20080193483A1 · Aug 14, 2008