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

广谱中和抗体 10-1074 的粘膜应用可保护恒河猴免受细胞相关的 SHIV 阴道暴露

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作者:Karunasinee Suphaphiphat, Delphine Desjardins, Valérie Lorin, Nastasia Dimant, Kawthar Bouchemal, Laetitia Bossevot, Maxence Galpin-Lebreau, Nathalie Dereuddre-Bosquet, Hugo Mouquet, Roger Le Grand, Mariangela Cavarelli

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.

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