3BNC117 a Broadly Neutralizing Antibody Suppresses Viremia in HIV-1-Infected Humans

By M. Caskey, F. Klein, J. C. Lorenzi, M. Seaman, A. West, Noreen Buckley, G. Kremer, Lilian Nogueira, Malte Braunschweig, J. Scheid and 15 more. Nature, 2015

725 citations recorded by the source corpus.

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.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging, Virology

View Paper: https://www.semanticscholar.org/paper/310d12207dd51d0b7f651007b532d70445d83557

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Citations in the corpus

Predicting evolution (2017, background): “In the coming years, we will have increasingly detailed and time-resolved data of evolutionary pressure and response, for example on immune response to infections by antigen-specific and broadly neutralizing antibodies 137 .”
Follicular Helper T Cells. (2016, background): “These bNAbs can suppress viremia in mice, macaques, and humans (1, 2).”