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

Marina Caskey, Florian Klein, Julio C.C. Lorenzi, Michael S. Seaman, Anthony P. West, Noreen Buckley, Gisela Kremer, Lilian Nogueira, Malte Braunschweig, Johannes F. Scheid, Joshua A. Horwitz, Irina Shimeliovich, Sivan Ben-Avraham, Maggi Witmer-Pack, Martin Platten, Clara Lehmann, Leah A. Burke, Thomas Hawthorne, Robert J. Gorelick, Bruce D. WalkerTibor Keler, Roy M. Gulick, Gerd Fätkenheuer, Sarah J. Schlesinger, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

495 Scopus citations

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 infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log 10 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.

Original languageEnglish
Pages (from-to)487-491
Number of pages5
JournalNature
Volume522
Issue number7557
DOIs
StatePublished - 8 Apr 2015
Externally publishedYes

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