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Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. 2017
Marina Caskey, and
Till Schoofs, and
Henning Gruell, and
Allison Settler, and
Theodora Karagounis, and
Edward F Kreider, and
Ben Murrell, and
Nico Pfeifer, and
Lilian Nogueira, and
Thiago Y Oliveira, and
Gerald H Learn, and
Yehuda Z Cohen, and
Clara Lehmann, and
Daniel Gillor, and
Irina Shimeliovich, and
Cecilia Unson-O'Brien, and
Daniela Weiland, and
Alexander Robles, and
Tim Kümmerle, and
Christoph Wyen, and
Rebeka Levin, and
Maggi Witmer-Pack, and
Kemal Eren, and
Caroline Ignacio, and
Szilard Kiss, and
Anthony P West, and
Hugo Mouquet, and
Barry S Zingman, and
Roy M Gulick, and
Tibor Keler, and
Pamela J Bjorkman, and
Michael S Seaman, and
Beatrice H Hahn, and
Gerd Fätkenheuer, and
Sarah J Schlesinger, and
Michel C Nussenzweig, and
Florian Klein
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.
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