Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers

Emilia Falkowska; Khoa M Le; Alejandra Ramos; Katie J Doores; Jeong Hyun Lee; Claudia Blattner; Alejandro Ramirez; Ronald Derking; Marit J van Gils; Chi-Hui Liang; Ryan Mcbride; Benjamin von Bredow; Sachin S Shivatare; Chung-Yi Wu; Po-Ying Chan-Hui; Yan Liu; Ten Feizi; Michael B Zwick; Wayne C Koff; Michael S Seaman; Kristine Swiderek; John P Moore; David Evans; James C Paulson; Chi-Huey Wong; Andrew B Ward; Ian A Wilson; Rogier W Sanders; Pascal Poignard; Dennis R Burton

doi:10.1016/j.immuni.2014.04.009

Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers

Immunity. 2014 May 15;40(5):657-68. doi: 10.1016/j.immuni.2014.04.009. Epub 2014 Apr 24.

Authors

Emilia Falkowska¹, Khoa M Le², Alejandra Ramos³, Katie J Doores⁴, Jeong Hyun Lee⁵, Claudia Blattner⁵, Alejandro Ramirez⁶, Ronald Derking⁷, Marit J van Gils⁷, Chi-Hui Liang², Ryan Mcbride⁸, Benjamin von Bredow⁹, Sachin S Shivatare¹⁰, Chung-Yi Wu¹⁰, Po-Ying Chan-Hui¹¹, Yan Liu¹², Ten Feizi¹², Michael B Zwick⁶, Wayne C Koff¹³, Michael S Seaman¹⁴, Kristine Swiderek¹¹, John P Moore¹⁵, David Evans⁹, James C Paulson¹⁶, Chi-Huey Wong¹⁰, Andrew B Ward⁵, Ian A Wilson¹⁷, Rogier W Sanders¹⁸, Pascal Poignard³, Dennis R Burton¹⁹

Affiliations

¹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA 02114, USA.
² Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK.
⁵ International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁶ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁷ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
⁸ Departments of Cell and Molecular Biology and Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53711, USA.
¹⁰ Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
¹¹ Theraclone Sciences, Inc., Seattle, Washington 98104, USA.
¹² Glycosciences Laboratory, Department of Medicine, Imperial College London, London W12 ONN, UK.
¹³ International AIDS Vaccine Initiative, New York, NY 10038, USA.
¹⁴ Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Boston, MA, 02215, USA.
¹⁵ Weill Medical College of Cornell University, New York, NY 10004, USA.
¹⁶ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹⁷ International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹⁸ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Weill Medical College of Cornell University, New York, NY 10004, USA.
¹⁹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, MA 02114, USA. Electronic address: burton@scripps.edu.

Abstract

Broadly neutralizing HIV antibodies are much sought after (a) to guide vaccine design, both as templates and as indicators of the authenticity of vaccine candidates, (b) to assist in structural studies, and (c) to serve as potential therapeutics. However, the number of targets on the viral envelope spike for such antibodies has been limited. Here, we describe a set of human monoclonal antibodies that define what is, to the best of our knowledge, a previously undefined target on HIV Env. The antibodies recognize a glycan-dependent epitope on the prefusion conformation of gp41 and unambiguously distinguish cleaved from uncleaved Env trimers, an important property given increasing evidence that cleavage is required for vaccine candidates that seek to mimic the functional HIV envelope spike. The availability of this set of antibodies expands the number of vaccine targets on HIV and provides reagents to characterize the native envelope spike.

Publication types

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

MeSH terms

Antibodies, Monoclonal / immunology*
Antibodies, Neutralizing / immunology*
Cell Line
Epitopes / immunology
HEK293 Cells
HIV Antibodies / immunology*
HIV Envelope Protein gp120 / immunology
HIV Envelope Protein gp41 / immunology*
HIV Envelope Protein gp41 / metabolism
HIV Infections / immunology
HIV Infections / prevention & control
HIV-1 / immunology
Humans
Molecular Sequence Data
Polysaccharides / immunology

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Epitopes
HIV Antibodies
HIV Envelope Protein gp120
HIV Envelope Protein gp41
Polysaccharides
gp41 protein, Human immunodeficiency virus 1

Associated data

GENBANK/KJ700282
GENBANK/KJ700283
GENBANK/KJ700284
GENBANK/KJ700285
GENBANK/KJ700286
GENBANK/KJ700287
GENBANK/KJ700288
GENBANK/KJ700289
GENBANK/KJ700290
GENBANK/KJ700291
GENBANK/KJ700292
GENBANK/KJ700293
GENBANK/KJ700294
GENBANK/KJ700295
GENBANK/KJ700296
GENBANK/KJ700297

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding