title: Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.
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 log10copies/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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Caskey
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Till
authors.initials: T
authors.lastname: Schoofs
authors.affiliation: Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.|German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gruell
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Settler
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Theodora
authors.initials: T
authors.lastname: Karagounis
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Edward F
authors.identifier: http://orcid.org/0000-0003-2330-8430
authors.initials: EF
authors.lastname: Kreider
authors.affiliation: Department of Medicine, University of California, San Diego, San Diego, California, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Murrell
authors.affiliation: Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
authors.forename: Nico
authors.identifier: http://orcid.org/0000-0002-4647-8566
authors.initials: N
authors.lastname: Pfeifer
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Lilian
authors.initials: L
authors.lastname: Nogueira
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Thiago Y
authors.initials: TY
authors.lastname: Oliveira
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Cohen
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.|German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gillor
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Shimeliovich
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Unson-O'Brien
authors.affiliation: Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.|German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weiland
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Robles
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kümmerle
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wyen
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Levin
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Maggi
authors.initials: M
authors.lastname: Witmer-Pack
authors.affiliation: Department of Biomedical Informatics, University of California, San Diego, San Diego, California, USA.|Bioinformatics and System Biology, University of California, San Diego, San Diego, California, USA.
authors.forename: Kemal
authors.initials: K
authors.lastname: Eren
authors.affiliation: Department of Medicine, University of California, San Diego, San Diego, California, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ignacio
authors.affiliation: Department of Ophthalmology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
authors.forename: Szilard
authors.initials: S
authors.lastname: Kiss
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.affiliation: Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.|Einstein/Rockefeller/CUNY Center for AIDS Research, Bronx, New York, USA.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Zingman
authors.affiliation: Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.affiliation: Celldex Therapeutics, Hampton, New Jersey, USA.
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.|German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.|Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.affiliation: Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.|German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D016466:CHO Cells; D003412:Cricetulus; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage* / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D010446:Peptide Fragments; D012367:RNA, Viral; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus