Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
AIDS Vaccines
/ immunology
Animals
Antibodies, Monoclonal
/ chemistry
Antibodies, Neutralizing
/ chemistry
Antibody Formation
/ immunology
Cryoelectron Microscopy
/ methods
Epitopes
/ chemistry
Glycosylation
HIV Antibodies
/ chemistry
HIV Infections
/ immunology
HIV-1
/ genetics
Humans
Macaca mulatta
Models, Molecular
Protein Conformation
env Gene Products, Human Immunodeficiency Virus
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 08 2021
10 08 2021
Historique:
received:
26
02
2021
accepted:
23
07
2021
entrez:
11
8
2021
pubmed:
12
8
2021
medline:
24
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34376662
doi: 10.1038/s41467-021-25087-4
pii: 10.1038/s41467-021-25087-4
pmc: PMC8355326
doi:
Substances chimiques
AIDS Vaccines
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Epitopes
0
HIV Antibodies
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4817Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136621
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : NIH HHS
ID : U42 OD011023
Pays : United States
Informations de copyright
© 2021. The Author(s).
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