Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial.
AIDS Vaccines
/ administration & dosage
Amino Acid Sequence
Antibody-Dependent Cell Cytotoxicity
Binding Sites, Antibody
Clinical Trials, Phase II as Topic
Crystallography, X-Ray
Double-Blind Method
Epitopes, T-Lymphocyte
/ chemistry
Fluorescence Resonance Energy Transfer
HIV Antibodies
/ chemistry
HIV Envelope Protein gp120
/ chemistry
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Randomized Controlled Trials as Topic
Vaccine Potency
RV144
human immunodeficiency virus
structural biology
vaccines
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
30 06 2020
30 06 2020
Historique:
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
10
4
2021
Statut:
epublish
Résumé
Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluorescence resonance energy transfer-fluorescence correlation spectroscopy to describe the molecular basis for epitopes of seven RV144 Abs and compared them to A32 and C11, C1/C2 Abs induced in HIV infection. Our data indicate that most vaccine Abs recognize the 7-stranded β-sandwich of gp120, a unique hybrid epitope bridging A32 and C11 binding sites. Although primarily directed at the 7-stranded β-sandwich, some accommodate the gp120 N terminus in C11-bound 8-stranded conformation and therefore recognize a broader range of CD4-triggered Env conformations. Our data also suggest that Abs of RV144 and RV305, the RV144 follow-up study, although likely initially induced by the ALVAC-HIV prime encoding full-length gp120, matured through boosting with truncated AIDSVAX gp120 variants.
Identifiants
pubmed: 32605979
pii: mBio.00208-20
doi: 10.1128/mBio.00208-20
pmc: PMC7327165
pii:
doi:
Substances chimiques
AIDS Vaccines
0
Epitopes, T-Lymphocyte
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150447
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI124912
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 Tolbert et al.
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