July 19, 2019  |  

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.

Authors: Caskey, Marina and Schoofs, Till and Gruell, Henning and Settler, Allison and Karagounis, Theodora and Kreider, Edward F and Murrell, Ben and Pfeifer, Nico and Nogueira, Lilian and Oliveira, Thiago Y and Learn, Gerald H and Cohen, Yehuda Z and Lehmann, Clara and Gillor, Daniel and Shimeliovich, Irina and Unson-O'Brien, Cecilia and Weiland, Daniela and Robles, Alexander and Kümmerle, Tim and Wyen, Christoph and Levin, Rebeka and Witmer-Pack, Maggi and Eren, Kemal and Ignacio, Caroline and Kiss, Szilard and West, Anthony P and Mouquet, Hugo and Zingman, Barry S and Gulick, Roy M and Keler, Tibor and Bjorkman, Pamela J and Seaman, Michael S and Hahn, Beatrice H and Fätkenheuer, Gerd and Schlesinger, Sarah J and Nussenzweig, Michel C and Klein, Florian

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.

Journal: Nature medicine
DOI: 10.1038/nm.4268
Year: 2017

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