Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein.
Amino Acid Sequence
Animals
Antibodies, Monoclonal
/ chemistry
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antigens, Viral
/ immunology
Binding Sites
Binding, Competitive
Brain
/ pathology
Chiroptera
/ virology
Cross Reactions
/ immunology
Crystallography, X-Ray
Ephrin-B2
/ metabolism
Female
Ferrets
/ virology
Hendra Virus
/ immunology
Henipavirus
/ immunology
Humans
Interferometry
Liver
/ pathology
Models, Molecular
Neutralization Tests
Nipah Virus
/ immunology
Protein Binding
Protein Conformation
Protein Domains
Receptors, Virus
/ chemistry
B lymphocytes
Hendra virus
Henipavirus infections
Nipah virus
antibodies
antigen-antibody reactions
epitopes
molecular structure
monoclonal
pre-exposure prophylaxis
receptor binding protein
therapy
viral
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 12 2020
10 12 2020
Historique:
received:
08
04
2020
revised:
04
10
2020
accepted:
12
11
2020
entrez:
11
12
2020
pubmed:
12
12
2020
medline:
19
5
2021
Statut:
ppublish
Résumé
Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.
Identifiants
pubmed: 33306954
pii: S0092-8674(20)31540-3
doi: 10.1016/j.cell.2020.11.023
pmc: PMC7771633
mid: NIHMS1647999
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Antigens, Viral
0
Ephrin-B2
0
Receptors, 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
Sous-ensembles de citation
IM
Pagination
1536-1550.e17Subventions
Organisme : NIAID NIH HHS
ID : F31 AI152332
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142764
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax, GigaGen, Meissa Vaccines; and is founder of IDBiologics, Inc. Vanderbilt University has applied for a patent related to antibodies described in this paper. All other authors declare no competing interests.
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