Influenza H7N9 Virus Neuraminidase-Specific Human Monoclonal Antibodies Inhibit Viral Egress and Protect from Lethal Influenza Infection in Mice.
Animals
Antibodies, Heterophile
/ pharmacology
Antibodies, Monoclonal
/ pharmacology
Antibodies, Neutralizing
/ pharmacology
Antibodies, Viral
/ pharmacology
Birds
Epitopes
/ immunology
Humans
Influenza A Virus, H7N9 Subtype
/ drug effects
Influenza Vaccines
/ immunology
Influenza in Birds
/ prevention & control
Influenza, Human
/ prevention & control
Mice
Neuraminidase
/ immunology
Orthomyxoviridae Infections
/ prevention & control
Pre-Exposure Prophylaxis
Vaccination
Vaccines, Inactivated
Viral Proteins
/ immunology
Virus Release
/ drug effects
B lymphocyte
H7N9
antibodies
epitopes
influenza A virus
monoclonal
neuraminidase
pre-exposure prophylaxis
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
11 12 2019
11 12 2019
Historique:
received:
17
06
2019
revised:
20
08
2019
accepted:
07
10
2019
pubmed:
24
11
2019
medline:
16
4
2020
entrez:
24
11
2019
Statut:
ppublish
Résumé
H7N9 avian influenza virus causes severe infections and might have the potential to trigger a major pandemic. Molecular determinants of human humoral immune response to N9 neuraminidase (NA) proteins, which exhibit unusual features compared with seasonal influenza virus NA proteins, are ill-defined. We isolated 35 human monoclonal antibodies (mAbs) from two H7N9 survivors and two vaccinees. These mAbs react to NA in a subtype-specific manner and recognize diverse antigenic sites on the surface of N9 NA, including epitopes overlapping with, or distinct from, the enzyme active site. Despite recognizing multiple antigenic sites, the mAbs use a common mechanism of action by blocking egress of nascent virions from infected cells, thereby providing an antiviral prophylactic and therapeutic protection in vivo in mice. Studies of breadth, potency, and diversity of antigenic recognition from four subjects suggest that vaccination with inactivated adjuvanted vaccine induce NA-reactive responses comparable to that of H7N9 natural infection.
Identifiants
pubmed: 31757769
pii: S1931-3128(19)30527-X
doi: 10.1016/j.chom.2019.10.003
pmc: PMC6941661
mid: NIHMS1545131
pii:
doi:
Substances chimiques
Antibodies, Heterophile
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Influenza Vaccines
0
Vaccines, Inactivated
0
Viral Proteins
0
Neuraminidase
EC 3.2.1.18
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
715-728.e8Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400024C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201300023C
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201300023I
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117905
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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