# US 10,307,477 B2 · Methods for inducing an immune response against human immunodeficiency virus infection in subjects undergoing antiretroviral treatment

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- Number: US 10,307,477 B2
- Document ID: US10307477B2
- Status: Granted
- Kind: B2
- Application number: 15/693,650
- Filed: 2017-09-01
- Published: 2018-03-08
- Granted: 2019-06-04
- Earliest claimed: 2016-09-02
- Assignees: Janssen Vaccines & Prevention B.V.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; Beth Israel Deaconess Medical Center, Inc.; The United States of America as represented by the Secretary of the Army
- Applicants: Janssen Vaccines & Prevention B.V.; Beth Israel Deaconess Medical Center, Inc.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc; The United States of America, AS Represented By the Secretary of the Army
- Inventors: Frank Tomaka; Maria Grazia Pau; Johanna Schuitemaker; Dan Barouch; Jintanat Ananworanich; Merlin Robb; Nelson L. Michael; Jerome Kim
- Web page: https://patentgrep.com/patent/US10307477B2

## CPC

- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61K 39/12: Viral antigens
- A61P 31/18: for HIV
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/575: {humoral response}
- A61K 2039/70: {Multivalent vaccine}
- C12N 2710/10043: viral genome or elements thereof as genetic vector
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- C12N 2710/24043: viral genome or elements thereof as genetic vector
- C12N 2710/24143: viral genome or elements thereof as genetic vector
- C12N 2740/16021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2740/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/16171: Demonstrated in vivo effect
- C12N 2740/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/16271: Demonstrated in vivo effect
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×1010 viral particles (vp).

### Claim 6 (depends on 3)

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.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the first and second MVA vectors are administered at a total dose of about 1×108 plaque forming units (pfu).

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 8)

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.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

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

### Claim 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.

### Claim 13 (depends on 12)

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.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×1010 vp.

### Claim 15 (depends on 12)

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.

### Claim 16 (depends on 12)

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

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 12)

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.

### Claim 19 (depends on 13)

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.

### Claim 20 (depends on 19)

The method according to claim 19, wherein the first, second, and third Ad26 vectors are administered at a total dose of about 5×1010 vp, and the first and second MVA vectors are administered at a total dose of about 1×108 pfu.