title: Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller.
abstract: Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env). One of the three, BG18, an antibody directed against the glycan-V3 portion of Env, is the most potent member of this class reported to date and, as revealed by crystallography and electron microscopy, recognizes HIV-1 Env in a manner that is distinct from other bNAbs in this class. Single-genome sequencing of HIV-1 from serum samples obtained over a period of 9 years showed a diverse group of circulating viruses, 88.5% (31 of 35) of which remained sensitive to at least one of the temporally coincident autologous bNAbs and the individual's serum. Thus, bNAb-sensitive strains of HIV-1 coexist with potent neutralizing antibodies that target the virus and may contribute to control in this individual. When administered as a mix, the three bNAbs controlled viremia in HIV-1YU2-infected humanized mice. Our finding suggests that combinations of bNAbs may contribute to control of HIV-1 infection.
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Natalia T
authors.initials: NT
authors.lastname: Freund
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Haoqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Scharf
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Lilian
authors.initials: L
authors.lastname: Nogueira
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Horwitz
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Jovana
authors.initials: J
authors.lastname: Golijanin
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Sievers
authors.affiliation: Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, MD 20742, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Cesar Lorenzi
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Halper-Stromberg
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02129, USA.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Toth
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02129, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Piechocka-Trocha
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gristick
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Marit J
authors.initials: MJ
authors.lastname: van Gils
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, MD 20742, USA.
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02129, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Gazumyan
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02129, USA.|Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.affiliation: Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA. nussen@rockefeller.edu.|Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism; D015331:Cohort Studies; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D019562:Viral Load; D014766:Viremia; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; C103707:HLA-B57 antigen; D054299:env Gene Products, Human Immunodeficiency Virus