title: Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates.
abstract: 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.
authors.affiliation: Université Côte d'Azur, Nice, France; CNRS UMR7275, IPMC, Valbonne, France.
authors.forename: Selma
authors.initials: S
authors.lastname: Bekri
authors.affiliation: Université Côte d'Azur, Nice, France; CNRS UMR7275, IPMC, Valbonne, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bourdely
authors.affiliation: Université Côte d'Azur, Nice, France; CNRS UMR7275, IPMC, Valbonne, France; INSERM, Paris, France.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Luci
authors.affiliation: CEA, Université Paris Sud, INSERM U1184 "Immunology of Viral Infections and Autoimmune Diseases" , Fontenay-aux-Roses , France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: INSERM, Unit 1109 INSERM/UNISTRA, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France; Beijing Key Laboratory for HIV/AIDS Research, Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.affiliation: CEA, Université Paris Sud, INSERM U1184 "Immunology of Viral Infections and Autoimmune Diseases" , Fontenay-aux-Roses , France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Martinon
authors.affiliation: Université Côte d'Azur, Nice, France; CNRS UMR7275, IPMC, Valbonne, France.
authors.forename: Véronique M
authors.initials: VM
authors.lastname: Braud
authors.affiliation: Departamento de Química Física e Instituto de Biotecnología, Universidad de Granada , Granada , Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Luque
authors.affiliation: Departamento de Química Física e Instituto de Biotecnología, Universidad de Granada , Granada , Spain.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Mateo
authors.affiliation: Departamento de Química Física e Instituto de Biotecnología, Universidad de Granada , Granada , Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Crespillo
authors.affiliation: Departamento de Química Física e Instituto de Biotecnología, Universidad de Granada , Granada , Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Conejero-Lara
authors.affiliation: INSERM, Unit 1109 INSERM/UNISTRA, Fédération de Médecine Translationnelle de Strasbourg , Strasbourg , France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.affiliation: CEA, Université Paris Sud, INSERM U1184 "Immunology of Viral Infections and Autoimmune Diseases" , Fontenay-aux-Roses , France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Université Côte d'Azur, Nice, France; CNRS UMR7275, IPMC, Valbonne, France; INSERM, Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Anjuère
keywords: B memory response; HIV; cholera toxin B subunit; mucosal antibodies; neutralization; sublingual immunization; trimeric gp41