Your browser doesn't support javascript.
loading
Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.
Caskey, Marina; Klein, Florian; Lorenzi, Julio C C; Seaman, Michael S; West, Anthony P; Buckley, Noreen; Kremer, Gisela; Nogueira, Lilian; Braunschweig, Malte; Scheid, Johannes F; Horwitz, Joshua A; Shimeliovich, Irina; Ben-Avraham, Sivan; Witmer-Pack, Maggi; Platten, Martin; Lehmann, Clara; Burke, Leah A; Hawthorne, Thomas; Gorelick, Robert J; Walker, Bruce D; Keler, Tibor; Gulick, Roy M; Fätkenheuer, Gerd; Schlesinger, Sarah J; Nussenzweig, Michel C.
Afiliação
  • Caskey M; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Klein F; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Lorenzi JC; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
  • West AP; Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
  • Buckley N; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Kremer G; 1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] Clinical Trials Center Cologne, ZKS Köln, BMBF 01KN1106, University of Cologne, Cologne, Germany.
  • Nogueira L; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Braunschweig M; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
  • Scheid JF; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Horwitz JA; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Shimeliovich I; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Ben-Avraham S; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Witmer-Pack M; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Platten M; 1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
  • Lehmann C; 1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
  • Burke LA; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10065, USA.
  • Hawthorne T; Celldex Therapeutics, Inc., Hampton, New Jersey 08827, USA.
  • Gorelick RJ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
  • Walker BD; Ragon Institute of MGH, MIT and Harvard, Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
  • Keler T; Celldex Therapeutics, Inc., Hampton, New Jersey 08827, USA.
  • Gulick RM; Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10065, USA.
  • Fätkenheuer G; 1] First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany [2] German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
  • Schlesinger SJ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Nussenzweig MC; 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
Nature ; 522(7557): 487-91, 2015 06 25.
Article em En | MEDLINE | ID: mdl-25855300
ABSTRACT
HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Carga Viral / Anticorpos Neutralizantes Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Idioma: En Revista: Nature Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Viremia / Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Carga Viral / Anticorpos Neutralizantes Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Idioma: En Revista: Nature Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos