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
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Nat Med. 2017 Feb;23(2):185-191. doi: 10.1038/nm.4268. Epub 2017 Jan 16.
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 log 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.
单克隆抗体10-1074靶向HIV-1包膜（Env）蛋白上的V3聚糖超位点。它是迄今为止分离出的最有效的抗HIV-1中和抗体之一。在此，我们报告了其在33名接受该抗体单次静脉输注的个体中的安全性和活性。10-1074耐受性良好，在未感染HIV-1的参与者中半衰期为24.0天，在感染HIV-1的个体中半衰期为12.8天。13名病毒血症患者接受了最高剂量30mg/kg的10-1074。其中11名参与者对10-1074敏感，病毒血症迅速下降，平均下降1.52 log拷贝/毫升。病毒学分析显示，输注后的头几周出现了多种独立的对10-1074耐药的病毒。新出现的逃逸变体通常对相关的V3特异性抗体PGT121耐药，但对靶向非重叠表位的抗体，如抗CD4结合位点抗体3BNC117和VRC01仍敏感。结果证明了10-1074在人体中的安全性和活性，并支持靶向V3聚糖超位点的抗体可能对治疗和预防HIV-1感染有用的观点。
