Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure

Karunasinee Suphaphiphat, Delphine Desjardins, Valérie Lorin, Nastasia Dimant, Kawthar Bouchemal, Laetitia Bossevot, Maxence Galpin-Lebreau, Nathalie Dereuddre-Bosquet, Hugo Mouquet, Roger Grand and Mariangela Cavarelli ()
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Karunasinee Suphaphiphat: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Delphine Desjardins: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Valérie Lorin: Université Paris Cité, INSERM U1222
Nastasia Dimant: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Kawthar Bouchemal: CNRS, Institut de Recherche de Chimie Paris, CNRS UMR 8247
Laetitia Bossevot: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Maxence Galpin-Lebreau: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Nathalie Dereuddre-Bosquet: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Hugo Mouquet: Université Paris Cité, INSERM U1222
Roger Grand: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
Mariangela Cavarelli: Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Passive immunization using broadly neutralizing antibodies (bNAbs) is investigated in clinical settings to inhibit HIV-1 acquisition due to the lack of a preventive vaccine. However, bNAbs efficacy against highly infectious cell-associated virus transmission has been overlooked. HIV-1 transmission mediated by infected cells present in body fluids likely dominates infection and aids the virus in evading antibody-based immunity. Here, we show that the anti-N-glycans/V3 loop HIV-1 bNAb 10-1074 formulated for topical vaginal application in a microbicide gel provides significant protection against repeated cell-associated SHIV162P3 vaginal challenge in non-human primates. The treated group has a significantly lower infection rate than the control group, with 5 out of 6 animals fully protected from the acquisition of infection. The findings suggest that mucosal delivery of potent bnAbs may be a promising approach for preventing transmission mediated by infected cells and support the use of anti-HIV-antibody-based strategies as potential microbicides in human clinical trials.

Date: 2023
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DOI: 10.1038/s41467-023-41966-4

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