| Literature DB >> 28092665 |
Marina Caskey1, Till Schoofs1, Henning Gruell2,3,4, Allison Settler1, Theodora Karagounis1, Edward F Kreider5, Ben Murrell6, Nico Pfeifer7, Lilian Nogueira1, Thiago Y Oliveira1, Gerald H Learn5, Yehuda Z Cohen1, Clara Lehmann3,4, Daniel Gillor3, Irina Shimeliovich1, Cecilia Unson-O'Brien1, Daniela Weiland2,3,4, Alexander Robles8, Tim Kümmerle3, Christoph Wyen3, Rebeka Levin1, Maggi Witmer-Pack1, Kemal Eren9,10, Caroline Ignacio6, Szilard Kiss11, Anthony P West12, Hugo Mouquet13, Barry S Zingman14,15, Roy M Gulick16, Tibor Keler17, Pamela J Bjorkman12, Michael S Seaman8, Beatrice H Hahn5, Gerd Fätkenheuer3,4, Sarah J Schlesinger1, Michel C Nussenzweig1,18, Florian Klein2,3,4.
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.Entities:
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Year: 2017 PMID： 28092665 PMCID： PMC5467219 DOI： 10.1038/nm.4268
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440