Caskey, Marina ORCID: 0000-0003-1727-8693, Schoofs, Till, Gruell, Henning, Settler, Allison, Karagounis, Theodora ORCID: 0000-0003-1481-9589, Kreider, Edward F., Murrell, Ben ORCID: 0000-0002-0393-4445, Pfeifer, Nico ORCID: 0000-0002-4647-8566, Nogueira, Lilian, Oliveira, Thiago Y., Learn, Gerald H., Cohen, Yehuda Z., Lehmann, Clara, Gillor, Daniel, Shimeliovich, Irma, Unson-O'Brien, Cecilia, Weiland, Daniela, Robles, Alexander, Kuemmerle, Tim, Wyen, Christoph, Levin, Rebeka, Witmer-Pack, Maggi, Eren, Kemal, Ignacio, Caroline, Kiss, Szilard ORCID: 0000-0003-3433-8432, West, Anthony P., Jr., Mouquet, Hugo ORCID: 0000-0002-4230-610X, Zingman, Barry S., Gulick, Roy M., Keler, Tibor, Bjorkman, Pamela J., Seaman, Michael S., Hahn, Beatrice H., Faetkenheuer, Gerd, Schlesinger, Sarah J., Nussenzweig, Michel C. and Kleine, Florian (2017). Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat. Med., 23 (2). S. 185 - 192. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-170X

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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 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Caskey, MarinaUNSPECIFIEDorcid.org/0000-0003-1727-8693UNSPECIFIED
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Settler, AllisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karagounis, TheodoraUNSPECIFIEDorcid.org/0000-0003-1481-9589UNSPECIFIED
Kreider, Edward F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murrell, BenUNSPECIFIEDorcid.org/0000-0002-0393-4445UNSPECIFIED
Pfeifer, NicoUNSPECIFIEDorcid.org/0000-0002-4647-8566UNSPECIFIED
Nogueira, LilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliveira, Thiago Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Learn, Gerald H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohen, Yehuda Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gillor, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shimeliovich, IrmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Unson-O'Brien, CeciliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiland, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robles, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuemmerle, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wyen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, RebekaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witmer-Pack, MaggiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eren, KemalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ignacio, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiss, SzilardUNSPECIFIEDorcid.org/0000-0003-3433-8432UNSPECIFIED
West, Anthony P., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mouquet, HugoUNSPECIFIEDorcid.org/0000-0002-4230-610XUNSPECIFIED
Zingman, Barry S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gulick, Roy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keler, TiborUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, Beatrice H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesinger, Sarah J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleine, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-241863
DOI: 10.1038/nm.4268
Journal or Publication Title: Nat. Med.
Volume: 23
Number: 2
Page Range: S. 185 - 192
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-170X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; HIV-1 VACCINE; GLYCAN RECOGNITION; PASSIVE TRANSFER; IN-VIVO; POTENT; VRC01; THERAPY; PHARMACOKINETICSMultiple languages
Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24186

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