Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.
CP: Immunology
X-ray crystallography
Zika virus
dengue virus
flavivirus
monoclonal antibodies
neutralizing antibodies
rhesus macaque
structural biology
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 Aug 2023
29 Aug 2023
Historique:
received:
02
11
2022
revised:
09
06
2023
accepted:
21
07
2023
pubmed:
10
8
2023
medline:
10
8
2023
entrez:
10
8
2023
Statut:
ppublish
Résumé
Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.
Identifiants
pubmed: 37561630
pii: S2211-1247(23)00953-1
doi: 10.1016/j.celrep.2023.112942
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112942Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests S.J.K., V.D., G.D., K.M., N.M., D.H.B., M.G.J., R.S.S., and R.G.J. are named inventors on a PCT patent application WO 2019/209974 describing ZIKV neutralizing antibodies and their use. D.H.B. has received grants from Novavax and personal fees from IGM Biosciences. M.H., A.A., E.D., and B.J.D. are employees of Integral Molecular. B.J.D. is also a shareholder of the company.