Methods for inducing an immune response against human immunodeficiency virus infection in subjects undergoing antiretroviral treatment
Inventors
TOMAKA, Frank • Pau, Maria Grazia • Schuitemaker, Johanna • BAROUCH, Dan • ANANWORANICH, Jintanat • ROBB, Merlin • MICHAEL, Nelson L. • Kim, Jerome
Assignees
Janssen Vaccines and Prevention BV • Beth Israel Deaconess Medical Center Inc • Henry M Jackson Foundation for Advancedment of Military Medicine Inc • Walter Reed Army Institute of Research • United States Department of the Army
Publication Number
US-10307477-B2
Publication Date
2019-06-04
Expiration Date
2037-09-01
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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.
Core Innovation
The invention relates to methods for inducing an immune response against human immunodeficiency virus (HIV) in HIV-infected subjects undergoing antiretroviral therapy (ART). The methods involve administering a primer vaccine comprising adenovirus 26 (Ad26) vectors encoding mosaic HIV antigens and a booster vaccine comprising modified vaccinia ankara (MVA) vectors encoding mosaic HIV antigens. This vaccination regimen is designed to enhance cellular immunity and induce therapeutic immunity against HIV infection.
The background identifies significant challenges associated with ART, including the need for lifelong adherence, side effects, drug resistance, and the high global costs of treatment. Although ART has saved millions of lives, it does not provide a cure. There is a need for alternative or complementary treatments, such as therapeutic vaccines, that can induce a functional cure and reduce or eliminate the need for lifelong ART by improving immune responses and enabling viral control even after ART interruption.
The invention addresses these challenges by using mosaic HIV antigens optimized to cover diverse HIV strains and epitopes, administered via prime-boost regimens using Ad26 and MVA vectors. These methods aim to induce broad, potent T-cell mediated immune responses in subjects who are on stable ART, particularly those who initiated ART during acute infection. As a result, the vaccine regimen can induce measurable immune responses that maintain viremic control after ART interruption, potentially achieving HIV remission or functional cure.
Claims Coverage
The claims cover two independent methods focused on inducing an immune response against HIV in infected subjects undergoing ART using specific vaccination regimens involving adenovirus 26 and modified vaccinia ankara vectors encoding mosaic HIV antigens. There are five main inventive features extracted from the claims.
Use of Ad26 vector primer vaccine encoding mosaic HIV gag, pol, and/or env antigens
Administering to an HIV-infected 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 together with a pharmaceutically acceptable carrier.
Use of MVA vector booster vaccine encoding mosaic HIV gag, pol, and/or env antigens
Administering to the 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 together with a pharmaceutically acceptable carrier.
Specified dosing schedule and re-administration timing
The booster vaccine is administered about 22-26 weeks after the initial primer vaccine. The primer vaccine can be re-administered about 10-14 weeks after the initial primer vaccine, and the booster vaccine can be re-administered about 46 to 50 weeks after the initial primer vaccine.
Specific mosaic HIV antigens defined by SEQ ID NOs and vector ratios and doses
The primer vaccine encodes three mosaic HIV antigens with amino acid sequences of SEQ ID NOs: 1, 3, and 4, delivered via three Ad26 vectors; the booster vaccine encodes four mosaic HIV antigens of SEQ ID NOs: 1, 2, 3, and 4, delivered via two MVA vectors encoding selected combinations of these antigens. The total dose of Ad26 vectors is about 5×10^10 viral particles; the total dose of MVA vectors is about 1×10^8 plaque forming units. The Ad26 vectors may be administered at a ratio of about 2:1:1 and the MVA vectors at about 1:1.
Interruption of ART after vaccination and maintenance of viral suppression
Discontinuing ART at about 10-14 weeks following the last booster vaccine administration, where subjects maintain viral suppression for at least 24 weeks after discontinuing ART, particularly when ART was initiated during acute HIV infection.
The claims describe a method using a prime-boost vaccine regimen with Ad26 and MVA vectors encoding specified mosaic HIV antigens administered on a defined schedule to HIV-infected subjects undergoing ART, with provisions for ART interruption and sustained viral control post-vaccination.
Stated Advantages
The vaccine regimen can induce a measurable immune response against HIV in subjects with fully suppressed HIV infection.
Therapeutic vaccine regimen may maintain viremic control after interruption of ART, addressing challenges linked to lifelong ART treatment including side effects, adherence, and costs.
Mosaic HIV antigens enhance the breadth and depth of T-cell epitope coverage, potentially improving immune control against diverse HIV strains and clades.
Use of Ad26 vectors offers low pre-existing immunity in populations enhancing vaccine efficacy.
MVA-based booster vaccines provide safety, industrial scalability, and the capacity to induce both humoral and cellular immune responses.
Documented Applications
Use as a therapeutic vaccine for HIV-infected subjects undergoing antiretroviral therapy, particularly those who initiated ART during acute HIV infection.
Vaccination regimens aimed at inducing immune responses to enable ART discontinuation (analytical treatment interruption) while maintaining viral suppression.
Clinical evaluation in human subjects for safety, immunogenicity, and efficacy in extending viremic control post-ART interruption.
Interested in licensing this patent?