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Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.
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.
Afiliação
  • Caskey M; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Schoofs T; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Gruell H; Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Settler A; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Karagounis T; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Kreider EF; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Murrell B; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Pfeifer N; Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Nogueira L; Department of Medicine, University of California, San Diego, San Diego, California, USA.
  • Oliveira TY; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
  • Learn GH; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Cohen YZ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Lehmann C; Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Gillor D; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Shimeliovich I; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Unson-O'Brien C; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Weiland D; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Robles A; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Kümmerle T; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Wyen C; Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Levin R; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Witmer-Pack M; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Eren K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • Ignacio C; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Kiss S; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • West AP; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Mouquet H; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • Zingman BS; Department of Biomedical Informatics, University of California, San Diego, San Diego, California, USA.
  • Gulick RM; Bioinformatics and System Biology, University of California, San Diego, San Diego, California, USA.
  • Keler T; Department of Medicine, University of California, San Diego, San Diego, California, USA.
  • Bjorkman PJ; Department of Ophthalmology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
  • Seaman MS; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
  • Hahn BH; Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.
  • Fätkenheuer G; Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
  • Schlesinger SJ; Einstein/Rockefeller/CUNY Center for AIDS Research, Bronx, New York, USA.
  • Nussenzweig MC; Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
  • Klein F; Celldex Therapeutics, Hampton, New Jersey, USA.
Nat Med ; 23(2): 185-191, 2017 Feb.
Article em En | MEDLINE | ID: mdl-28092665
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Anticorpos Anti-HIV / Infecções por HIV / Anticorpos Neutralizantes / Anticorpos Monoclonais Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Anticorpos Anti-HIV / Infecções por HIV / Anticorpos Neutralizantes / Anticorpos Monoclonais Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article