Antiviral vaccines with improved cellular immunogenicity

• US 9,017,691 B2
• Filed: 11/18/2009
• Issued: 04/28/2015
• Est. Priority Date: 11/18/2008
• Status: Active Grant

• Current Assignee: BETH Israel Deaconess Medical Center (Caregroup Incorporated), Los Alamos National Security LLC (Government of the United States of America)
• Original Assignee: BETH Israel Deaconess Medical Center (Caregroup Incorporated), Los Alamos National Security LLC (Government of the United States of America)
• Inventors: Barouch, Dan H., Korber, Bette T., Fischer, William M.
• Primary Examiner(s): Lucas, Zachariah
• Assistant Examiner(s): SNYDER, STUART
• Application Number:
  US13/130,018
• Publication Number:
  US 20120076812A1
• Time in Patent Office: 1,987 Days
• Field of Search: None
• US Class Current: 424/188.1
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/235 Adenoviridae
• CPC Class Codes: A61K 39/275 Poxviridae, e.g. avipoxvirus
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2710/10043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/24043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16171 Demonstrated in vivo effect
• CPC Class Codes: C12N 2740/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16271 Demonstrated in vivo effect
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16334 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compositions, methods, and kits for the treatment or prevention of viral infections. The polyvalent (e.g., 2-valent) vaccines described herein incorporate computationally-optimized viral polypeptides that can increase the diversity or breadth and depth of cellular immune response in vaccinated subjects.

Claims

1. An immunogenic composition comprising at least two distinct optimized viral polypeptides, wherein said optimized viral polypeptides correspond to the same viral gene product, wherein the viral gene product is selected from the group consisting of gag, pol, and env, and

wherein the at least two distinct optimized gag polypeptides are selected from any one or more of the groups:

(a) SEQ ID NO;

3 and 4, (b) SEQ ID NO;

3, and 15 (c) SEQ ID NO;

4 and 15;

wherein the at least two distinct optimized pol polypeptides are selected from any one or more of the groups;

(a) SEQ ID NO;

12 and 13, (b) SEQ ID NO;

12 and 14, (c) SEQ ID NO;

13 and 14; and

wherein the at least two distinct optimized env polypeptides are selected from any one or more of the groups;

(a) SEQ ID NO;

9 and 10, (b) SEQ ID NO;

9 and 11, (c) SEQ ID NO;

10 and 11.

2. The immunogenic composition of claim 1, wherein said mammal is a human.

3. The immunogenic composition of claim 1, wherein said immunogenic composition elicits a cellular immune response against said viral gene product.

4. The immunogenic composition of claim 1, wherein said at least two optimized gag viral polypeptides comprise an amino acid sequence having the sequences set forth in each of SEQ ID NO:

3 and 4.

5. The immunogenic composition of claim 1, wherein said at least two optimized pol viral polypeptides comprise an amino acid sequence having the sequences set forth in each of SEQ ID NO:

12 and 13.

6. The immunogenic composition of claim 4 further comprising at least two optimized pol viral polypeptides, wherein said polypeptides comprise an amino acid sequence having the sequences set forth in each of SEQ ID NO:

12 and 13.

7. The immunogenic composition of claim 6 further comprising at least two optimized env viral polypeptides, wherein said polypeptides comprise an amino acid sequence having the sequences set forth in each of SEQ ID NO:

9 and 10.

8. The immunogenic composition of claim 1, wherein said at least two distinct optimized viral polypeptides are encoded in a viral vector selected from the group consisting of adenovirus serotype 26 (Ad26), adenovirus serotype 34 (Ad34), adenovirus serotype 35 (Ad35), adenovirus serotype 48 (Ad48), er adenovirus serotype 5 HVR48 (Ad5HVR48), poxvirus, and modified vaccinia virus Ankara (MVA).

9. A method for inducing an HIV-1-specific immune response in a mammal comprising administering to said mammal the immunogenic composition of claim 1.

10. A method of manufacturing the immunogenic composition of claim 1 comprising synthesizing said optimized viral polypeptides and combining said optimized viral polypeptides with a pharmaceutically acceptable carrier.

11. A kit comprising:

a) the immunogenic composition of claim 1;

b) a pharmaceutically acceptable carrier, excipient, or diluent;

c) instructions for the use thereof; and

, optionally,

d) an adjuvant.

12. The immunogenic composition of claim 8, wherein said vector is the Ad26 vector.

13. The immunogenic composition of claim 8, wherein said vector is the MVA vector.

14. The immunogenic composition of claim 1 admixed with a pharmaceutically acceptable carrier, excipient, or diluent.

15. The immunogenic composition of claim 1, wherein said at least two optimized env viral polypeptides comprise an amino acid sequence having the sequences set forth in each of SEQ ID NO:

9 and 11.

16. A method for inducing an HIV-1-specific immune response in a mammal comprising administering to said mammal the immunogenic composition of claim 8.

17. The method of claim 16, wherein said vector is the Ad26 vector.

18. The method of claim 16, wherein said vector is the MVA vector.

23. The method of claim 16, wherein said mammal is a human.

19. A polypeptide comprising the amino acid sequence of SEQ ID NO:

9.

20. A method for inducing an HIV-1-specific immune response in a mammal comprising administering to said mammal the immunogenic composition of claim 19.

21. The method of claim 20, wherein the mammal is a human.

22. The method of claim 21, wherein said composition comprises a pharmaceutically acceptable carrier, excipient, or diluent.