Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers.
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.
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.
Emilia
E
Falkowska
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.
Khoa M
KM
Le
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.
Alejandra
A
Ramos
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.
Katie J
KJ
Doores
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.
Jeong Hyun
JH
Lee
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.
Claudia
C
Blattner
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Alejandro
A
Ramirez
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Ronald
R
Derking
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Marit J
MJ
van Gils
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.
Chi-Hui
CH
Liang
Departments of Cell and Molecular Biology and Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ryan
R
Mcbride
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53711, USA.
Benjamin
B
von Bredow
Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
Sachin S
SS
Shivatare
Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
Chung-Yi
CY
Wu
Theraclone Sciences, Inc., Seattle, Washington 98104, USA.
Po-Ying
PY
Chan-Hui
Glycosciences Laboratory, Department of Medicine, Imperial College London, London W12 ONN, UK.
Yan
Y
Liu
Glycosciences Laboratory, Department of Medicine, Imperial College London, London W12 ONN, UK.
Ten
T
Feizi
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Michael B
MB
Zwick
International AIDS Vaccine Initiative, New York, NY 10038, USA.
Wayne C
WC
Koff
Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Boston, MA, 02215, USA.
Michael S
MS
Seaman
Theraclone Sciences, Inc., Seattle, Washington 98104, USA.
Kristine
K
Swiderek
Weill Medical College of Cornell University, New York, NY 10004, USA.
John P
JP
Moore
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53711, USA.
David
D
Evans
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
James C
JC
Paulson
Genomics Research Center, Academia Sinica, Nankang, Taipei 115, Taiwan.
Chi-Huey
CH
Wong
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.
Andrew B
AB
Ward
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.
Ian A
IA
Wilson
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.
Rogier W
RW
Sanders
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.
Pascal
P
Poignard
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.
Dennis R
DR
Burton
D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011134:Polysaccharides; C514787:gp41 protein, Human immunodeficiency virus 1