Antibody 10-1074 suppresses viremia in HIV-1-infected individuals
Marina Caskey,Till Schoofs,Henning Gruell,Allison Settler,Theodora K. Karagounis,Edward F. Kreider,Ben Murrell,Nico Pfeifer,Lilian Nogueira,Thiago Y. Oliveira,Gerald H. Learn,Yehuda Z. Cohen,Clara Lehmann,Daniel Gillor,Irina Shimeliovich,Cecilia Unson-O’Brien,Daniela Weiland,Alexander. Robles,Tim Kümmerle,Christoph Wyen,Rebeka Levin,Maggi Witmer-Pack,Kemal Eren,Caroline Ignacio,Szilard Kiss,Anthony P. West,Hugo Mouquet,Barry S. Zingman,Barry S. Zingman,Roy M. Gulick,Tibor Keler,Pamela J. Bjorkman,Michael S. Seaman,Beatrice H. Hahn,Gerd Fätkenheuer,Sarah J. Schlesinger,Michel C. Nussenzweig,Michel C. Nussenzweig,Florian Klein +38 more
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TLDR
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.Abstract:
Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge. 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.read more
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Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.
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Combination therapy with anti-HIV-1 antibodies maintains viral suppression
Pilar Mendoza,Henning Gruell,Lilian Nogueira,Joy A. Pai,Allison L. Butler,Katrina G. Millard,Clara Lehmann,Isabelle Suárez,Thiago Y. Oliveira,Julio C. C. Lorenzi,Yehuda Z. Cohen,Christoph Wyen,Christoph Wyen,Tim Kümmerle,Tim Kümmerle,Theodora K. Karagounis,Ching-Lan Lu,Lisa Handl,Cecilia Unson-O’Brien,Roshni Patel,Carola Ruping,Maike Schlotz,Maggi Witmer-Pack,Irina Shimeliovich,Gisela Kremer,Eleonore Thomas,Kelly E. Seaton,Jill Horowitz,Anthony P. West,Pamela J. Bjorkman,Georgia D. Tomaras,Roy M. Gulick,Nico Pfeifer,Gerd Fätkenheuer,Michael S. Seaman,Florian Klein,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +38 more
TL;DR: It is concluded that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.
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