Methods for inducing an immune response against human immunodeficiency virus infection in subjects undergoing antiretroviral treatment

Patent metadata

Field	Value
Publication number	US-10307477-B2
Application number	US-201715693650-A
Country	US
Kind code	B2
Filing date	Sep 1, 2017
Priority date	Sep 2, 2016
Publication date	Jun 4, 2019
Grant date	Jun 4, 2019

Abstract

Methods for inducing an immune response against Human Immunodeficiency Virus (HIV) in HIV-infected subjects undergoing antiretroviral therapy (ART) are described. The methods include administering an adenovirus vector primer vaccine and a modified vaccinia virus (MVA) vector booster vaccine encoding mosaic HIV antigens.

First claim

What is claimed is:

1. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising:
(i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of one or more adenovirus 26 (Ad26) vectors encoding one or more mosaic HIV gag, pol and/or env antigens and a pharmaceutically acceptable carrier; and
(ii) administering to the human subject a booster vaccine comprising an immunogenically effective amount of one or more modified vaccinia ankara (MVA) vectors encoding one or more mosaic HIV gag, pol and/or env antigens and a pharmaceutically acceptable carrier.

2. The method of claim 1 , wherein the booster vaccine is administered about 22-26 weeks after the primer vaccine is initially administered.

3. The method according to claim 1 , wherein the primer vaccine comprises Ad26 vectors encoding three mosaic HIV antigens having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4; and the booster vaccine comprises MVA vectors encoding four mosaic HIV antigens having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

4. The method according to claim 3 , wherein the immunogenically effective amount of the Ad26 vectors encoding mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 consists of three Ad26 vectors of which a first Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 4.

5. The method according to claim 4 , wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10 10 viral particles (vp).

6. The method according to claim 3 , wherein the immunogenically effective amount of the MVA vectors encoding mosaic HIV antigens of SEQ ID NOs: 1, 2, 3, and 4 consists of two MVA vectors of which a first MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 2 and 4.

7. The method according to claim 6 , wherein the first and second MVA vectors are administered at a total dose of about 1×10 8 plaque forming units (pfu).

8. The method according to claim 1 , further comprising re-administering the primer vaccine at about 10-14 weeks after the primer vaccine is initially administered; and re-administering the booster vaccine at about 46 to 50 weeks after the primer vaccine is initially administered.

9. The method according to claim 8 , wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.

10. The method according to claim 1 , wherein the human subject initiated ART during acute HIV infection.

11. The method according to claim 1 , wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.

12. A method of inducing an immune response against a human immunodeficiency virus (HIV) in an HIV-infected human subject undergoing antiretroviral therapy (ART), the method comprising:
(i) administering to the human subject a primer vaccine comprising an immunogenically effective amount of one or more adenovirus 26 (Ad26) vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1, 3, and 4 and a pharmaceutically acceptable carrier; and
(ii) administering to the human subject a booster composition comprising an immunogenically effective amount of one or more MVA vectors encoding one or more mosaic HIV antigens comprising the amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4 and a pharmaceutically acceptable carrier,
wherein the primer vaccine is re-administered at about 10-14 weeks after the primer vaccine is initially administered; the booster vaccine is first administered at about 22-26 weeks after the primer vaccine is initially administered; and the booster vaccine is re-administered at about 46-50 weeks after primer vaccine is initially administered; and
wherein the human subject initiated ART during acute HIV infection.

13. The method according to claim 12 , wherein the immunogenically effective amount of the Ad26 vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 consists of three Ad26 vectors of which a first Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 1, a second Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 3, and a third Ad26 vector encodes mosaic HIV antigen of SEQ ID NO: 4.

14. The method according to claim 13 , wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10 10 vp.

15. The method according to claim 12 , wherein the primer vaccine is re-administered at about 12 weeks after the primer vaccine is initially administered, the booster vaccine is first administered at about 24 weeks after the primer vaccine is initially administered, and the booster vaccine is re-administered at about 48 weeks after the primer vaccine is initially administered.

16. The method according to claim 12 , wherein the ART is discontinued at about 10-14 weeks after the last booster vaccine is administered.

17. The method according to claim 1 , wherein a human subject to which the primer vaccine and the booster vaccine has been administered, discontinues ART and maintains viral suppression for at least 24 weeks after discontinuing ART.

18. The method according to claim 12 , wherein a human subject to which the primer vaccine and the booster vaccine has been administered, discontinues ART and maintains viral suppression for at least 24 weeks after discontinuing ART.

19. The method according to claim 13 , wherein the immunogenically effective amount of the MVA vectors encoding one or more mosaic HIV antigens of SEQ ID NOs: 1-4 consists of two MVA vectors of which a first MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 1 and 3, and a second MVA vector encodes mosaic HIV antigens of SEQ ID NOs: 2 and 4.

20. The method according to claim 19 , wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×10 10 vp, and the first and second MVA vectors are administered at a total dose of about 1×10 8 pfu.

Assignees

• Janssen Vaccines & Prevention Bv
• Beth Israel Deaconess Medical Ct Inc
• Henry M Jackson Found For The Advancement Of Military Medicine Inc
• Us Army
• Henry M Jackson Found Advancement Military Medicine Inc

Inventors

• Tomaka Frank
• Pau Maria Grazia
• Schuitemaker Johanna
• Barouch Dan
• Ananworanich Jintanat
• Robb Merlin
• Michael Nelson L
• Kim Jerome

Classifications

• C12N2740/16021

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• A61K2039/57

  characterised by the type of response, e.g. Th1, Th2 · CPC title

• C12N2740/16034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2710/24143

  viral genome or elements thereof as genetic vector · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title