HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers

Rogier W Sanders; Marit J van Gils; Ronald Derking; Devin Sok; Thomas J Ketas; Judith A Burger; Gabriel Ozorowski; Albert Cupo; Cassandra Simonich; Leslie Goo; Heather Arendt; Helen J Kim; Jeong Hyun Lee; Pavel Pugach; Melissa Williams; Gargi Debnath; Brian Moldt; Mariëlle J van Breemen; Gözde Isik; Max Medina-Ramírez; Jaap Willem Back; Wayne C Koff; Jean-Philippe Julien; Eva G Rakasz; Michael S Seaman; Miklos Guttman; Kelly K Lee; Per Johan Klasse; Celia LaBranche; William R Schief; Ian A Wilson; Julie Overbaugh; Dennis R Burton; Andrew B Ward; David C Montefiori; Hansi Dean; John P Moore

doi:10.1126/science.aac4223

HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers

Science. 2015 Jul 10;349(6244):aac4223. doi: 10.1126/science.aac4223. Epub 2015 Jun 18.

Authors

Rogier W Sanders¹, Marit J van Gils², Ronald Derking², Devin Sok³, Thomas J Ketas⁴, Judith A Burger², Gabriel Ozorowski⁵, Albert Cupo⁴, Cassandra Simonich⁶, Leslie Goo⁶, Heather Arendt⁷, Helen J Kim⁵, Jeong Hyun Lee⁵, Pavel Pugach⁴, Melissa Williams⁴, Gargi Debnath⁴, Brian Moldt³, Mariëlle J van Breemen², Gözde Isik², Max Medina-Ramírez², Jaap Willem Back⁸, Wayne C Koff⁷, Jean-Philippe Julien⁵, Eva G Rakasz⁹, Michael S Seaman¹⁰, Miklos Guttman¹¹, Kelly K Lee¹¹, Per Johan Klasse⁴, Celia LaBranche¹², William R Schief¹³, Ian A Wilson¹⁴, Julie Overbaugh⁶, Dennis R Burton¹⁵, Andrew B Ward⁵, David C Montefiori¹², Hansi Dean⁷, John P Moore¹⁶

Affiliations

¹ 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.
² Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
³ 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.
⁴ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
⁵ 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.
⁶ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁷ International AIDS Vaccine Initiative, New York, NY 10004, USA.
⁸ Pepscan Therapeutics, 8243RC Lelystad, Netherlands.
⁹ Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
¹⁰ 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.
¹¹ Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
¹² Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
¹³ 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.
¹⁴ 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.
¹⁵ 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.
¹⁶ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA. jpm2003@med.cornell.edu rws2002@med.cornell.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

AIDS Vaccines / immunology*
Animals
Antibodies, Neutralizing / immunology*
Cross Reactions
Epitopes / immunology
HIV Antibodies / immunology*
HIV Infections / prevention & control*
HIV-1 / immunology*
Humans
Macaca
Protein Engineering
Protein Multimerization
Rabbits
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / immunology
env Gene Products, Human Immunodeficiency Virus / chemistry
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
Antibodies, Neutralizing
Epitopes
HIV Antibodies
Recombinant Proteins
env Gene Products, Human Immunodeficiency Virus
gp140 envelope protein, Human immunodeficiency virus 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding