期刊
NATURE MEDICINE
卷 23, 期 2, 页码 185-191出版社
NATURE PORTFOLIO
DOI: 10.1038/nm.4268
关键词
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资金
- Translational Virology Core at the UC San Diego Center for AIDS Research [P30 AI036214]
- NIH/NIGMS [U01 GM110749]
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) Grants [OPP1032144, OPP1092074, OPP1124068]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health Grant [HIVRAD P01 AI100148]
- BEAT-HIV Delaney grant [UM1 AI126620]
- Robertson Foundation
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663-01]
- German Research Foundation [SCHO 1612/1-1]
- National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- German Center for Infection Research (DZIF)
- Ruth L. Kirschstein National Research Service Award [F30 AI112426]
- National Institute of Allergy and Infectious Diseases [R00 AI120851]
- National Library of Medicine [T15 LM007092]
- Heisenberg Program of the DFG [KL 2389/2-1]
- European Research Council [ERC-StG639961]
- German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
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 logic 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.
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