Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.

TitleViraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.
Publication TypeJournal Article
Year of Publication2015
AuthorsCaskey M, Klein F, Lorenzi JCC, Seaman MS, West AP, Buckley N, Kremer G, Nogueira L, Braunschweig M, Scheid JF, Horwitz JA, Shimeliovich I, Ben-Avraham S, Witmer-Pack M, Platten M, Lehmann C, Burke LA, Hawthorne T, Gorelick RJ, Walker BD, Keler T, Gulick RM, Fätkenheuer G, Schlesinger SJ, Nussenzweig MC
JournalNature
Volume522
Issue7557
Pagination487-91
Date Published2015 Jun 25
ISSN1476-4687
Abstract

HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

DOI10.1038/nature14411
Alternate JournalNature
PubMed ID25855300
Grant ListHHSN261200800001E / / PHS HHS / United States
U19AI111825-01 / AI / NIAID NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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