Durable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodies

David A. Garber (), Debra R. Adams, Patricia Guenthner, James Mitchell, Kristen Kelley, Till Schoofs, Anna Gazumyan, Martha Nason, Michael S. Seaman, Janet McNicholl, Michel C. Nussenzweig and Walid Heneine
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David A. Garber: Centers for Disease Control and Prevention
Debra R. Adams: Centers for Disease Control and Prevention
Patricia Guenthner: Centers for Disease Control and Prevention
James Mitchell: Centers for Disease Control and Prevention
Kristen Kelley: Centers for Disease Control and Prevention
Till Schoofs: The Rockefeller University
Anna Gazumyan: The Rockefeller University
Martha Nason: National Institutes of Health
Michael S. Seaman: Harvard Medical School
Janet McNicholl: Centers for Disease Control and Prevention
Michel C. Nussenzweig: The Rockefeller University
Walid Heneine: Centers for Disease Control and Prevention

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 μg ml−1 correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.

Date: 2020
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DOI: 10.1038/s41467-020-16928-9

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