4.8 Article

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

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NATURE COMMUNICATIONS
卷 14, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-023-41966-4

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This study demonstrates that mucosal delivery of the bNAb 10-1074 in a microbicide gel can effectively inhibit cell-associated transmission of HIV-1 in non-human primates. The findings suggest that this approach has potential as a preventive strategy against infection mediated by infected cells.
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. HIV-1 can be transmitted by infected cells in body fluids and an efficient prophylaxis should prevent this. Here the authors show that the HIV-1 antibody 10-1074, when applied as topical vaginal gel, inhibits cell-associated transmission in non-human primates.

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