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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Nature Communications, Volume 12, No. 1, Article 4817, Year 2021
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Description
Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic. © 2021, The Author(s).
Authors & Co-Authors
Antanasijevic, Aleksandar
United States, San Diego
Scripps Research Institute
Bhiman, Jinal N.
United States, San Diego
Scripps Research Institute
LaBranche, Celia C.
United States, Durham
Duke University Medical Center
Allen, Joel D.
United Kingdom, Southampton
University of Southampton
Rantalainen, Kimmo
United States, San Diego
Scripps Research Institute
Berndsen, Zachary T.
United States, San Diego
Scripps Research Institute
Baker, David James
United States, Seattle
University of Washington
United States, Chevy Chase
Howard Hughes Medical Institute
King, Neil P.
United States, Seattle
University of Washington
Sanders, Rogier W.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
United States, Ithaca
Cornell University
Moore, John Philip
United States, Ithaca
Cornell University
Crotty, Shane
United States, San Diego
La Jolla Institute for Immunology
Crispin, Max D.
United Kingdom, Southampton
University of Southampton
Montefiori, David Charles
United States, Durham
Duke University Medical Center
Burton, Dennis Raymond
United States, San Diego
Scripps Research Institute
Schief, William R.
United States, San Diego
Scripps Research Institute
Silvestri, Guido
United States, Atlanta
Emory University
Ward, Andrew B.
United States, San Diego
Scripps Research Institute
Statistics
Citations: 33
Authors: 17
Affiliations: 9
Identifiers
Doi:
10.1038/s41467-021-25087-4
ISSN:
20411723
Research Areas
Infectious Diseases