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Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates

2017; Frontiers Media; Volume: 8; Linguagem: Inglês

10.3389/fimmu.2017.00063

1664-3224

Selma Bekri, Pierre Bourdely, Carmelo Luci, Nathalie Dereuddre‐Bosquet, Bin Su, Frédéric Martinon, Véronique M. Braud, Irene Luque, Pedro L. Mateo, Sara Crespillo, Francisco Conejero‐Lara, Christiane Moog, Roger Le Grand, Fabienne Anjuère,

T-cell and B-cell Immunology

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 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 sublingual 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 sublingual/intramuscular immunization with such muco-adhesive gp41-based vaccine elicited mucosal HIV-specific IgG and IgA antibodies more efficiently than intramuscular immunization alone. This strategy increased the number and duration of gp41-specific IgA secreting cells. Importantly, combined immunization improved the generation of functional antibodies three months after vaccination as detected in HIV-neutralizing assays. Therefore, sublingual immunization represents a promising vaccine strategy to block HIV-1 transmission.