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Nat Med. 2017 Feb;23(2):185-191. doi: 10.1038/nm.4268. Epub 2017 Jan 16.

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

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
2
Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
3
Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
4
German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
5
Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
6
Department of Medicine, University of California, San Diego, San Diego, California, USA.
7
Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
9
Department of Biomedical Informatics, University of California, San Diego, San Diego, California, USA.
10
Bioinformatics and System Biology, University of California, San Diego, San Diego, California, USA.
11
Department of Ophthalmology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
12
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
13
Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.
14
Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
15
Einstein/Rockefeller/CUNY Center for AIDS Research, Bronx, New York, USA.
16
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
17
Celldex Therapeutics, Hampton, New Jersey, USA.
18
Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.

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.

PMID:
28092665
PMCID:
PMC5467219
DOI:
10.1038/nm.4268
[Indexed for MEDLINE]
Free PMC Article

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