title: An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability.
abstract: The induction by vaccination of broadly neutralizing antibodies (bNAbs) capable of neutralizing various HIV-1 viral strains is challenging, but understanding how a subset of HIV-infected individuals develops bNAbs may guide immunization strategies. Here, we describe the isolation and characterization of the bNAb ACS202 from an elite neutralizer that recognizes a new, trimer-specific and cleavage-dependent epitope at the gp120-gp41 interface of the envelope glycoprotein (Env), involving the glycan N88 and the gp41 fusion peptide. In addition, an Env trimer, AMC011 SOSIP.v4.2, based on early virus isolates from the same elite neutralizer, was constructed, and its structure by cryo-electron microscopy at 6.2 Å resolution reveals a closed, pre-fusion conformation similar to that of the BG505 SOSIP.664 trimer. The availability of a native-like Env trimer and a bNAb from the same elite neutralizer provides the opportunity to design vaccination strategies aimed at generating similar bNAbs against a key functional site on HIV-1.
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Marit J
authors.initials: MJ
authors.lastname: van Gils
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Tom L G M
authors.initials: TL
authors.lastname: van den Kerkhof
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ozorowski
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Christopher A
authors.identifier: http://orcid.org/0000-0002-3364-3083
authors.initials: CA
authors.lastname: Cottrell
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauthner
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Pallesen
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Val
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Anila
authors.initials: A
authors.lastname: Yasmeen
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Steven W
authors.initials: SW
authors.lastname: de Taeye
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Schorcht
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gumbs
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Inez
authors.initials: I
authors.lastname: Johanna
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Saye-Francisco
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Chi-Hui
authors.initials: CH
authors.lastname: Liang
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Landais
authors.affiliation: Department of Immunology and Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Pritchard
authors.affiliation: Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Max
authors.initials: M
authors.lastname: Crispin
authors.affiliation: Department of Immunology and Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Janssen Pharmaceutical Companies of Johnson &Johnson, Archimedesweg 4-6, 2301 CA, Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Per Johan
authors.initials: PJ
authors.lastname: Klasse
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.affiliation: Department of Immunology and Microbial Science, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.|Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts 02139, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.|Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D020285:Cryoelectron Microscopy; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D019302:HIV Envelope Protein gp160 / Q000276:immunology / Q000648:ultrastructure; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; C514797:gp160 protein, Human immunodeficiency virus 1