Ad26 Based Therapeutic Vaccines for HIV
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Principal Investigator: Dan H. Barouch Organization: BETH ISRAEL DEACONESS MEDICAL CENTER Fiscal Year: 2024 Award: $1,503,450 Funding agency: National Institute of Allergy and Infectious Diseases The goal of therapeutic vaccination is to increase host immune control of HIV-1 to achieve durable virologic control in the absence of ART, which is defined as a “functional cure”. However, therapeutic vaccine studies in humans have to date been largely unsuccessful. We speculate that this may reflect the fact that prior vaccines (i) have failed to induce sufficient breadth of cellular immune responses and (ii) have not effectively activated or targeted the latent viral reservoir. We hypothesize that a therapeutic vaccine that induces potent and broad immune responses and that activates the latent viral reservoir will reduce the size of the replication- competent viral reservoir and will enhance virologic control following ART discontinuation. We have shown that Ad26/MVA therapeutic vaccination together with innate immune stimulation with a TLR7 agonist resulted in virologic control in a subset of SIV-infected rhesus monkeys following ART discontinuation. We therefore propose to evaluate the immunogenicity and efficacy of the Ad26/MVA + TLR7 agonist vaccine in HIV-1-infected humans to define its ability to control viral replication following discontinuation of ART. We also hypothesize that the addition of broadly neutralizing antibodies (bNAbs) may augment the antiviral efficacy of a therapeutic vaccine. To optimize both active and passive immunity, we propose a follow-up study to evaluate the optimal therapeutic vaccine together with bNAbs in HIV-1-infected humans. We therefore propose the following two Specific Aims: Specific Aim 1. To evaluate the safety, immunogenicity, and efficacy of Ad26/MVA therapeutic vaccination with TLR7 agonist administration in HIV-1-infected humans Specific Aim 2. To evaluate the safety, immunogenicity, and efficacy of Ad26/MVA therapeutic vaccination with broadly neutralizing antibodies (bNAbs) and a TLR7 agonist in HIV-1-infected humans Terms: <Active immunity><Acute><Agonist><Animals><Antigenic Determinants><Antigens><Binding Determinants><Bio-Informatics><Bioinformatics><Boston><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><Cell Body><Cells><Cellular Expansion><Cellular Growth><Chronic><Collaborations><Data><Epitopes><Evaluation><Follow-Up Studies><Followup Studies><Goals><HIV vaccine><HIV-1><HIV-I><HIV/AIDS Vaccines><HIV1><Human><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Immune><Immune Cell Activation><Immune response><Immunes><Immunologic Stimulation><Immunological Stimulation><Immunological response><Immunostimulation><Individual><Infection><M mulatta><M. mulatta><Macaca mulatta><Modern Man><Nature><Passive Immunity><Predisposition><Regimen><Rhesus Macaque><Rhesus Monkey><SIV><Safety><Simian Immunodeficiency Viruses><Susceptibility><T4 Cells><T4 Lymphocytes><TLR7><TLR7 gene><Testing><Thailand><Therapeutic><Therapeutic Effect><Toll-Like Receptor 7><VAC-TX><Vaccinated><Vaccine Clinical Trial><Vaccine Therapy><Vaccines><Viral Burden><Viral Latency><Viral Load><Viral Load result><Viral reservoir><Virus Latency><Virus Replication><Virus reservoir><acute infection><anti-viral efficacy><cell growth><design><designing><evaluate vaccines><host response><human immunodeficiency virus vaccine><immune activation><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><manufacture><mosaic><neutralizing antibody><prophylactic><therapeutic vaccination><therapeutic vaccine><treatment vaccines><vaccination study><vaccination trial><vaccine evaluation><vaccine for the treatment><vaccine for treatment><vaccine screening><vaccine study><vaccine testing><vaccine trial><vector><viral multiplication><viral replication><virus multiplication>