Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.
AIDS Vaccines
/ immunology
Antibodies, Monoclonal
/ immunology
Antibody Formation
/ immunology
Antibody Specificity
/ immunology
Antibody-Dependent Cell Cytotoxicity
/ immunology
Epitopes
/ immunology
HIV Antibodies
/ immunology
HIV Envelope Protein gp120
/ immunology
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Immunization, Secondary
/ methods
Immunoglobulin G
/ immunology
HIV vaccine
antibody function
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 01 2020
31 01 2020
Historique:
received:
11
07
2019
accepted:
25
10
2019
pubmed:
30
11
2019
medline:
22
8
2020
entrez:
29
11
2019
Statut:
epublish
Résumé
Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) monoclonal antibodies (MAbs) frequently mediate potent antibody-dependent cellular cytotoxicity (ADCC), making them an important vaccine target. Here, we explore the effect of delayed and repetitive boosting of RV144 vaccine recipients with AIDSVAX B/E on the C1C2-specific MAb repertoire. It was found that boosting increased clonal lineage-specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific MAb showed that it bound a highly conserved Env gp120 epitope. Thus, boosting to affinity mature these types of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than that seen in the RV144 trial.
Identifiants
pubmed: 31776278
pii: JVI.01120-19
doi: 10.1128/JVI.01120-19
pmc: PMC6997759
pii:
doi:
Substances chimiques
AIDS Vaccines
0
AIDSVAX
0
AIDSVAX B-E
0
Antibodies, Monoclonal
0
Epitopes
0
HIV Antibodies
0
HIV Envelope Protein gp120
0
Immunoglobulin G
0
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI129769
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR007592
Pays : United States
Organisme : NIH HHS
ID : K01 OD024877
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116274
Pays : United States
Informations de copyright
Copyright © 2020 Easterhoff et al.
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