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dc.contributor.authorChua, Joel V
dc.contributor.authorDavis, Charles
dc.contributor.authorHusson, Jennifer S
dc.contributor.authorNelson, Amy
dc.contributor.authorPrado, Ilia
dc.contributor.authorFlinko, Robin
dc.contributor.authorLam, Ka Wing J
dc.contributor.authorMutumbi, Lydiah
dc.contributor.authorMayer, Bryan T
dc.contributor.authorDong, Dan
dc.contributor.authorFulp, William
dc.contributor.authorMahoney, Celia
dc.contributor.authorGerber, Monica
dc.contributor.authorGottardo, Raphael
dc.contributor.authorGilliam, Bruce L
dc.contributor.authorGreene, Kelli
dc.contributor.authorGao, Hongmei
dc.contributor.authorYates, Nicole
dc.contributor.authorFerrari, Guido
dc.contributor.authorTomaras, Georgia
dc.contributor.authorMontefiori, David
dc.contributor.authorSchwartz, Jennifer A
dc.contributor.authorFouts, Timothy
dc.contributor.authorDeVico, Anthony L
dc.contributor.authorLewis, George K
dc.contributor.authorGallo, Robert C
dc.contributor.authorSajadi, Mohammad M
dc.date.accessioned2021-06-22T13:46:53Z
dc.date.available2021-06-22T13:46:53Z
dc.date.issued2021-06-04
dc.identifier.urihttp://hdl.handle.net/10713/16063
dc.description.abstractA major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult volunteers in this first-in-human phase 1a randomized, double-blind, placebo-controlled study with three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. The overall incidence of adverse events (AEs) was not significantly different between vaccinees and controls. The majority (89%) of vaccine-related AE were mild. The most common vaccine-related adverse event was injection site pain. There were no vaccine-related serious AE, discontinuation due to AE, intercurrent HIV infection, or significant decreases in CD4 count. By the final vaccination, all vaccine recipients developed antibodies against IHV01 and demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 vaccine was safe, well tolerated, and immunogenic at all doses tested. The vaccine raised broadly reactive humoral responses against conserved CD4i epitopes on gp120 that mediates antiviral functions.en_US
dc.description.urihttps://doi.org/10.1016/j.vaccine.2021.05.090en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.relation.ispartofVaccineen_US
dc.rightsCopyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.en_US
dc.subjectCD4ien_US
dc.subjectChimeric subunit vaccineen_US
dc.subjectFull-length single chain (FLSC)en_US
dc.subjectHIVen_US
dc.subjectVaccineen_US
dc.titleSafety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trialen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.vaccine.2021.05.090
dc.identifier.pmid34099328
dc.source.volume39
dc.source.issue29
dc.source.beginpage3879
dc.source.endpage3891
dc.source.countryNetherlands


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