Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection.
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
16
04
2020
revised:
07
07
2020
accepted:
10
07
2020
entrez:
26
8
2020
pubmed:
26
8
2020
medline:
21
10
2020
Statut:
ppublish
Résumé
Human cytomegalovirus (HCMV) is the most common congenital infection. A glycoprotein B (gB) subunit vaccine (gB/MF59) is the most efficacious clinically tested to date, having achieved 50% protection against primary infection of HCMV-seronegative women. We previously identified that gB/MF59 vaccination primarily elicits non-neutralizing antibody responses, with variable binding to gB genotypes, and protection associated with binding to membrane-associated gB. We hypothesized that gB-specific non-neutralizing antibody binding breadth and function are dependent on epitope and genotype specificity, and ability to interact with membrane-associated gB. We mapped twenty-four gB-specific monoclonal antibodies (mAbs) from naturally HCMV-infected individuals for gB domain specificity, genotype preference, and ability to mediate phagocytosis or NK cell activation. gB-specific mAbs were primarily specific for Domain II and demonstrated variable binding to gB genotypes. Two mAbs facilitated phagocytosis with binding specificities of Domain II and AD2. This investigation provides novel understanding on the relationship between gB domain specificity and antigenic variability on gB-specific antibody effector functions.
Identifiants
pubmed: 32838941
pii: S0042-6822(20)30136-7
doi: 10.1016/j.virol.2020.07.009
pmc: PMC7447913
mid: NIHMS1616994
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
182-191Subventions
Organisme : NIH HHS
ID : K01 OD024877
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI136556
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI147992
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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