title: HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers.
abstract: A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands. jpm2003@med.cornell.edu rws2002@med.cornell.edu.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ 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, 1105 AZ Amsterdam, Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Derking
authors.affiliation: Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ketas
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Burger
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ozorowski
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Cupo
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Simonich
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Goo
authors.affiliation: International AIDS Vaccine Initiative, New York, NY 10004, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Arendt
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pugach
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Williams
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Gargi
authors.initials: G
authors.lastname: Debnath
authors.affiliation: Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
authors.forename: Mariëlle J
authors.initials: MJ
authors.lastname: van Breemen
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
authors.forename: Gözde
authors.initials: G
authors.lastname: Isik
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Medina-Ramírez
authors.affiliation: Pepscan Therapeutics, 8243RC Lelystad, Netherlands.
authors.forename: Jaap Willem
authors.initials: JW
authors.lastname: Back
authors.affiliation: International AIDS Vaccine Initiative, New York, NY 10004, USA.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Julien
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Miklos
authors.initials: M
authors.lastname: Guttman
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Per Johan
authors.initials: PJ
authors.lastname: Klasse
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, New York, NY 10004, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Schief
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.affiliation: Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Boston, MA 02114, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: International AIDS Vaccine Initiative, New York, NY 10004, USA.
authors.forename: Hansi
authors.initials: H
authors.lastname: Dean
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. jpm2003@med.cornell.edu rws2002@med.cornell.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008251:Macaca; D015202:Protein Engineering; D055503:Protein Multimerization; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1