Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges |
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Authors: | Bomsel Morgane Tudor Daniela Drillet Anne-Sophie Alfsen Annette Ganor Yonatan Roger Marie-Gaëlle Mouz Nicolas Amacker Mario Chalifour Anick Diomede Lorenzo Devillier Gilles Cong Zhe Wei Qiang Gao Hong Qin Chuan Yang Gui-Bo Zurbriggen Rinaldo Lopalco Lucia Fleury Sylvain |
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Institution: | 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 |
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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. |
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