Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
Abstract
A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan–targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for envelope (Env) glycoprotein variants with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (58)
Ashwin N. Skelly
Harry B. Gristick
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Hui Li
Edem Gavor
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Andrew J. Connell
Edward F. Kreider
Lorie Marchitto
Michael P. Hogarty
Maddy L. Newby
School of Biological Sciences, University of Southampton, Southampton, UK.
Joel D. Allen
School of Biological Sciences, University of Southampton, Southampton, UK.
Weimin Liu
Anthony P. West
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Kasirajan Ayyanathan
Mary S. Campion
Kaitlyn Winters
Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Colette G. Gordon
Rebecca A. Osbaldeston
Macy J. Akeley
Emily Lewis
Yingying Li
Ajay Singh
Kendra Cruickshank
Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Younghoon Park
Chengyan Zhao
Xuduo Li
Khaled Amereh
Elizabeth Van Itallie
Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
John W. Carey
Amie Albertus
Andrew T. DeLaitsch
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Jennifer R. Keeffe
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Melinda G. Lituchy
Agnes A. Walsh
Daniel J. Morris
Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rumi Habib
Frederic Bibollet-Ruche
Nitesh Mishra
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Gabriel Avillion
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA, USA.
Nicholas S. Koranda
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Samantha J. Plante
Christian L. Martella
Jinery Lora
Eric J. D. Wang
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Mark G. Lewis
Bioqual, Inc., Rockville, MD, USA.
Malcolm A. Martin
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Michel C. Nussenzweig
Michael S. Seaman
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Darrell J. Irvine
Kevin J. Wiehe
Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Barton F. Haynes
Kshitij Wagh
Bette Korber
Los Alamos National Laboratory, Los Alamos, NM, USA.
Raiees Andrabi
Max Crispin
School of Biological Sciences, University of Southampton, Southampton, UK.
Drew Weissman
Pamela J. Bjorkman
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Beatrice H. Hahn
George M. Shaw