Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase.
Humans
Influenza, Human
/ prevention & control
Influenza Vaccines
Neuraminidase
Orthomyxoviridae Infections
/ prevention & control
Influenza A Virus, H3N2 Subtype
Epitopes
Antibodies, Viral
Antibodies, Monoclonal
Influenza A Virus, H1N1 Subtype
Vaccination
Hemagglutinin Glycoproteins, Influenza Virus
antibody
cross-reactive
cryo-EM
influenza virus
neuraminidase
protective
structures
vaccination
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
received:
01
11
2022
revised:
19
07
2023
accepted:
10
10
2023
pmc-release:
14
11
2024
medline:
27
11
2023
pubmed:
16
11
2023
entrez:
15
11
2023
Statut:
ppublish
Résumé
There is growing appreciation for neuraminidase (NA) as an influenza vaccine target; however, its antigenicity remains poorly characterized. In this study, we isolated three broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, including one that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Although these three antibodies have diverse germline usages, they recognize similar epitopes that are distant from the NA active site and instead involve the highly conserved underside of NA head domain. We also showed that all three antibodies confer prophylactic and therapeutic protection in vivo, due to both Fc effector functions and NA inhibition through steric hindrance. Additionally, the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provide important insights into the development of a broadly protective influenza vaccine.
Identifiants
pubmed: 37967533
pii: S1074-7613(23)00445-4
doi: 10.1016/j.immuni.2023.10.005
pmc: PMC10655865
mid: NIHMS1939738
pii:
doi:
Substances chimiques
Influenza Vaccines
0
Neuraminidase
EC 3.2.1.18
Epitopes
0
Antibodies, Viral
0
Antibodies, Monoclonal
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2621-2634.e6Subventions
Organisme : NIAID NIH HHS
ID : U01 AI150747
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI165475
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI141990
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI144616
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00051
Pays : United States
Organisme : NCCIH NIH HHS
ID : DP2 AT011966
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93021C00014
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests N.C.W. consults for HeliXon. The Ellebedy laboratory received funding under sponsored research agreements from Moderna, Emergent BioSolutions, and AbbVie that are unrelated to the data presented in this study. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting. A.J.S., J.S.T., and A.H.E. are recipients of a licensing agreement with AbbVie that is unrelated to the data presented in this study. The Icahn School of Medicine at Mount Sinai has filed patent application on influenza virus vaccines that name F.K. as inventor. In addition, F.K. is currently consulting for Pfizer, Third Rock Ventures, and Avimex and has received support for vaccine research and development by Pfizer, GSK, and Dynavax.
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