Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.
Клиническое исследование I фазыСтатьяНазвание и аннотация: Перевод в очереди
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Caskey Marina, Schoofs Till, Gruell Henning, Settler Allison, Karagounis Theodora, Kreider Edward F, Murrell Ben, Pfeifer Nico, Nogueira Lilian, Oliveira Thiago Y, Learn Gerald H, Cohen Yehuda Z, Lehmann Clara, Gillor Daniel, Shimeliovich Irina, Unson-O'Brien Cecilia, Weiland Daniela, Robles Alexander, Kümmerle Tim, Wyen Christoph, Levin Rebeka, Witmer-Pack Maggi, Eren Kemal, Ignacio Caroline, Kiss Szilard, West Anthony P, Mouquet Hugo, Zingman Barry S, Gulick Roy M, Keler Tibor, Bjorkman Pamela J, Seaman Michael S, Hahn Beatrice H, Fätkenheuer Gerd, Schlesinger Sarah J, Nussenzweig Michel C, Klein Florian
Аннотация
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.