title: Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges.
abstract: Human immunodeficiency virus (HIV)-1 is mainly transmitted mucosally during sexual intercourse. We therefore evaluated the protective efficacy of a vaccine active at mucosal sites. Macaca mulatta monkeys were immunized via both the intramuscular and intranasal routes with an HIV-1 vaccine made of gp41-subunit antigens grafted on virosomes, a safe delivery carrier approved in humans with self-adjuvant properties. Six months after 13 vaginal challenges with simian-HIV (SHIV)-SF162P3, four out of five vaccinated animals remained virus-negative, and the fifth was only transiently infected. None of the five animals seroconverted to p27gag-SIV. In contrast, all 6 placebo-vaccinated animals became infected and seroconverted. All protected animals showed gp41-specific vaginal IgAs with HIV-1 transcytosis-blocking properties and vaginal IgGs with neutralizing and/or antibody-dependent cellular-cytotoxicity activities. In contrast, plasma IgGs totally lacked virus-neutralizing activity. The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS.
authors.affiliation: Mucosal Entry of HIV-1 and Mucosal Immunity, Cell Biology and Host Pathogen Interactions Department, Cochin Institute, CNRS (UMR 8104), 22 rue Méchain, Paris, France. morgane.bomsel@inserm.fr
authors.forename: Morgane
authors.initials: M
authors.lastname: Bomsel
authors.forename: Daniela
authors.initials: D
authors.lastname: Tudor
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Drillet
authors.forename: Annette
authors.initials: A
authors.lastname: Alfsen
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Ganor
authors.forename: Marie-Gaëlle
authors.initials: MG
authors.lastname: Roger
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mouz
authors.forename: Mario
authors.initials: M
authors.lastname: Amacker
authors.forename: Anick
authors.initials: A
authors.lastname: Chalifour
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Diomede
authors.forename: Gilles
authors.initials: G
authors.lastname: Devillier
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Gui-Bo
authors.initials: GB
authors.lastname: Yang
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Zurbriggen
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fleury
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001665:Binding Sites; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D006679:HIV Seropositivity; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D008253:Macaca mulatta / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D057900:Transcytosis; D014621:Vagina / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D022701:Virosomes / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000032:analysis
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C534067:HIV-1 envelope protein gp41 (649-683); D010446:Peptide Fragments; D022701:Virosomes; D054301:gag Gene Products, Human Immunodeficiency Virus; C074737:p27 gag protein, Human immunodeficiency virus