title: Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.
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.
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Marina
authors: M
authors: Caskey
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Florian
authors: F
authors: Klein
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Julio C C
authors: JC
authors: Lorenzi
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors: Michael S
authors: MS
authors: Seaman
authors: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
authors: Anthony P
authors: AP
authors: West
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Noreen
authors: N
authors: Buckley
authors: 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.
authors: Gisela
authors: G
authors: Kremer
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Lilian
authors: L
authors: Nogueira
authors: 1] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA [2] Albert Ludwigs University of Freiburg, 79085 Freiburg, Germany.
authors: Malte
authors: M
authors: Braunschweig
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Johannes F
authors: JF
authors: Scheid
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Joshua A
authors: JA
authors: Horwitz
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Irina
authors: I
authors: Shimeliovich
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Sivan
authors: S
authors: Ben-Avraham
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Maggi
authors: M
authors: Witmer-Pack
authors: 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.
authors: Martin
authors: M
authors: Platten
authors: 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.
authors: Clara
authors: C
authors: Lehmann
authors: 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.
authors: Leah A
authors: LA
authors: Burke
authors: Celldex Therapeutics, Inc., Hampton, New Jersey 08827, USA.
authors: Thomas
authors: T
authors: Hawthorne
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors: Robert J
authors: RJ
authors: Gorelick
authors: Ragon Institute of MGH, MIT and Harvard, Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
authors: Bruce D
authors: BD
authors: Walker
authors: Celldex Therapeutics, Inc., Hampton, New Jersey 08827, USA.
authors: Tibor
authors: T
authors: Keler
authors: Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10065, USA.
authors: Roy M
authors: RM
authors: Gulick
authors: 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.
authors: Gerd
authors: G
authors: Fätkenheuer
authors: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
authors: Sarah J
authors: SJ
authors: Schlesinger
authors: 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.
authors: Michel C
authors: MC
authors: Nussenzweig
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D019143:Evolution, Molecular; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000628:therapy* / Q000821:virology; D055815:Young Adult
chemical_list: C000599675:3BNC117 antibody; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120