An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes.
BG505
antibody immunotherapy
deep mutational scanning
immune escape
mutational antigenic profiling
virus evolution
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
19 02 2019
19 02 2019
Historique:
received:
31
08
2018
revised:
16
11
2018
accepted:
14
12
2018
pubmed:
3
2
2019
medline:
14
8
2019
entrez:
3
2
2019
Statut:
ppublish
Résumé
Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus's envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs's independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.
Identifiants
pubmed: 30709739
pii: S1074-7613(18)30565-X
doi: 10.1016/j.immuni.2018.12.017
pmc: PMC6435357
mid: NIHMS1517127
pii:
doi:
Substances chimiques
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
Pagination
520-532.e3Subventions
Organisme : NIAID NIH HHS
ID : R01 AI140891
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDA NIH HHS
ID : DP1 DA039543
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120961
Pays : United States
Organisme : NIH HHS
ID : S10 OD020069
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141707
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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