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 • United States Department of the Army
Publication Number
US-10525123-B2
Publication Date
2020-01-07
Expiration Date
2037-09-01
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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 include 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.
The problem being solved arises from the challenges of initiating and maintaining lifelong ART, which requires near perfect adherence and carries short-term and long-term side effects. ART also places significant economic and logistical pressure on health systems, particularly in developing countries. Moreover, drug resistance increases with prolonged treatment. Therefore, an alternative or complementary treatment, such as a therapeutic vaccine that can induce a functional cure or reduce the need for lifelong ART, is highly desirable.
Existing studies indicated the importance of inducing broad and potent immune responses against diverse HIV strains, especially T-cell based immunity using mosaic antigens. There is also evidence that therapeutic vaccines could re-stimulate antiviral CD8+ cytotoxic T lymphocytes to control virus reservoirs and prevent viral rebound after treatment interruptions. Despite prior therapeutic vaccine efforts, there remains a need for improved methods to enhance immune responses in HIV-infected subjects on ART to achieve viral suppression without continuous therapy.
Claims Coverage
The patent contains several independent claims focusing on methods of inducing an immune response against HIV in HIV-infected subjects undergoing ART by administering Ad26 adenovirus vector primer vaccines and MVA vector booster vaccines encoding mosaic HIV antigens.
Use of adenovirus 26 vectors encoding mosaic HIV antigens as primer vaccines
Administering to the HIV-infected subject undergoing ART a primer vaccine comprising immunogenically effective amounts of Ad26 vectors encoding mosaic HIV gag, pol, and/or env antigens, specifically those comprising amino acid sequences of SEQ ID NOs: 1, 3, and 4.
Use of modified vaccinia ankara vectors encoding mosaic HIV antigens as booster vaccines
Administering to the HIV-infected subject a booster vaccine comprising immunogenically effective amounts of MVA vectors encoding mosaic HIV gag, pol, and/or env antigens, including amino acid sequences of SEQ ID NOs: 1-4.
Specific dosing and scheduling of prime-boost regimen
The primer vaccine is re-administered at about 10-14 weeks after initial administration; the booster vaccine is first administered at about 22-26 weeks after the primer vaccine; and the booster vaccine is re-administered at about 46-50 weeks after the primer vaccine.
Inclusion of subjects who initiated ART during acute HIV infection
The method is particularly defined for subjects who started ART at least four weeks prior to primer vaccine administration and may have initiated ART during acute HIV infection with sustained viremic control prior to vaccination.
Specific vector compositions and ratios
The primer vaccine includes three Ad26 vectors encoding mosaic HIV antigens of SEQ ID NOs: 1, 3, and 4 administered at a total dose of about 5×10¹⁰ viral particles; the booster vaccine includes two MVA vectors encoding mosaic HIV antigens of SEQ ID NOs: 1 and 3, and SEQ ID NOs: 2 and 4, respectively, administered at about 1×10⁸ plaque forming units.
Discontinuation of ART following vaccination
The method contemplates discontinuing ART approximately 10-14 weeks after the last booster vaccine administration, with potential administration of activators of latent HIV reservoirs after ART interruption.
The claims cover a method of inducing an immune response in HIV-infected subjects undergoing ART using a prime-boost vaccine regimen with Ad26 and MVA vectors encoding mosaic HIV antigens, with specified dosing, timing, and subject characteristics, including possible ART discontinuation after immunization.
Stated Advantages
The vaccine regimen induces a measurable immune response and can maintain viremic control after ART interruption.
Using mosaic HIV antigens optimizes T-cell epitope coverage, potentially improving the breadth and efficacy of the immune response.
The prime-boost strategy using Ad26 and MVA vectors combines safety, manufacturing feasibility, and effective induction of cellular and humoral immunity.
The methods may reduce or eliminate the need for lifelong ART, alleviating burden on patients and healthcare systems.
Documented Applications
Therapeutic vaccination of HIV-infected human subjects undergoing antiretroviral therapy to induce immune responses against HIV.
Administration of the vaccine regimen to subjects who initiated ART during acute HIV infection to maintain viral suppression and allow analytical treatment interruption (ATI).
Clinical use in subjects on stable ART with suppressed viral loads to generate sustained viremic control post-ART discontinuation.
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