Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates
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AuthorBekri, Selma; Bourdely, Pierre; Luci, Carmelo; Dereuddre-Bosquet, Nathalie; Su, Bin; Martinon, Fréderic; Braud, Véronique M.; Luque Fernández, Irene; Mateo Alarcón, Pedro Luis; Crespillo, Sara; Conejero-Lara, Francisco; Moog, Christiane; Grand, Roger Le; Anjuère, Fabienne
Sublingual immunizationMucosal antibodiesB Memory responseNeutralizationHIVTrimeric gp41Cholera toxin B subunit
Bekri, S.; et al. Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates. Frontiers in Immunology, 8: 63 (2017). [http://hdl.handle.net/10481/45202]
SponsorshipThese studies were supported by Institut National de la Santé et de la Recherche Médicale (INSERM, France) by Centre National de Recherche Scientifique (CNRS, France), by the Agence Nationale de Recherche sur le SIDA (France), the SIDACTION (France), by the Euroneut-41 European Consortium (FP7 program), by the National Research Agency (ANR) through the “Investments for the Future” LABEX SIGNALIFE (ANR-11-LABX-0028-01) and the “Investments for the future” under Grant ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure and ANR-10-EQPX-02-01 funding the FlowCyTech facility.
Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention. Combined SL/intramuscular (IM) immunization with such mucoadhesive gp41-based vaccine elicited mucosal HIV-specific IgG and IgA antibodies more efficiently than IM immunization alone. This strategy increased the number and duration of gp41-specific IgA secreting cells. Importantly, combined immunization improved the generation of functional antibodies 3 months after vaccination as detected in HIV-neutralizing assays. Therefore, SL immunization represents a promising vaccine strategy to block HIV-1 transmission.