Autologous Antibody Responses to an HIV Envelope Glycan Hole Are Not Easily Broadened in Rabbits

Author:

Yang Yuhe R.123,McCoy Laura E.4,van Gils Marit J.5,Andrabi Raiees236,Turner Hannah L.123,Yuan Meng123,Cottrell Christopher A.123,Ozorowski Gabriel123ORCID,Voss James236,Pauthner Matthias236,Polveroni Thomas M.123,Messmer Terrence236,Wilson Ian A.1237,Sanders Rogier W.58,Burton Dennis R.236,Ward Andrew B.1239ORCID

Affiliation:

1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA

2. Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, USA

3. IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California, USA

4. Division of Infection and Immunity, University College London, London, United Kingdom

5. Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

6. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA

7. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA

8. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA

9. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, USA

Abstract

A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer-immunized rabbits. Our high-resolution cryo-electron microscopy (cryoEM) studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing prime-boost immunogens remains difficult.

Funder

HHS | National Institutes of Health

amfAR, The Foundation for AIDS Research

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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