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


ABSTRACT: 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.

SUBMITTER: Caskey M 

PROVIDER: S-EPMC5467219 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Caskey Marina M   Schoofs Till T   Gruell Henning H   Settler Allison A   Karagounis Theodora T   Kreider Edward F EF   Murrell Ben B   Pfeifer Nico N   Nogueira Lilian L   Oliveira Thiago Y TY   Learn Gerald H GH   Cohen Yehuda Z YZ   Lehmann Clara C   Gillor Daniel D   Shimeliovich Irina I   Unson-O'Brien Cecilia C   Weiland Daniela D   Robles Alexander A   Kümmerle Tim T   Wyen Christoph C   Levin Rebeka R   Witmer-Pack Maggi M   Eren Kemal K   Ignacio Caroline C   Kiss Szilard S   West Anthony P AP   Mouquet Hugo H   Zingman Barry S BS   Gulick Roy M RM   Keler Tibor T   Bjorkman Pamela J PJ   Seaman Michael S MS   Hahn Beatrice H BH   Fätkenheuer Gerd G   Schlesinger Sarah J SJ   Nussenzweig Michel C MC   Klein Florian F  

Nature medicine 20170116 2


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 dos  ...[more]

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2010-12-28 | GSE25456 | GEO