Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination.
CP: Immunology
FcR effector function
animal model
antibody responses
coronavirus
correlates of protection
cross-protection
pan-coronavirus vaccine
sarbecovirus
systems serology
vaccine development
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
25 04 2023
25 04 2023
Historique:
received:
18
10
2022
revised:
21
12
2022
accepted:
17
03
2023
medline:
4
10
2023
pubmed:
1
4
2023
entrez:
31
3
2023
Statut:
ppublish
Résumé
Group 2B β-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes in both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clade 2 bat sarbecovirus challenge models. The spike vaccines tested primarily elicit a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. Rather, non-neutralizing antibody functions, mechanistically linked to FcgR4 and spike S2, mediate cross-protection in wild-type mice. Protection is lost in FcR knockout mice, further supporting a model for non-neutralizing, protective antibodies. These data highlight the importance of FcR-mediated cross-protective immune responses in universal pan-sarbecovirus vaccine designs.
Identifiants
pubmed: 37000623
pii: S2211-1247(23)00337-6
doi: 10.1016/j.celrep.2023.112326
pmc: PMC10063157
pii:
doi:
Substances chimiques
Viral Vaccines
0
Antibodies, Viral
0
Antibodies, Neutralizing
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112326Subventions
Organisme : NIAID NIH HHS
ID : U19 AI135995
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007419
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146785
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA260543
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00052
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA260476
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI080289
Pays : United States
Organisme : NIH HHS
ID : K01 OD026529
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI042790
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI165072
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI158571
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests G.A. is a founder/equity holder in Seroymx Systems and Leyden Labs. G.A. has served as a scientific advisor for Sanofi Vaccines. G.A. has collaborative agreements with GSK, Merck, Abbvie, Sanofi, Medicago, BioNtech, Moderna, BMS, Novavax, SK Biosciences, Gilead, and Sanaria. R.S.B. has served as a consultant for Takeda and Sanofi Pasteur vaccines and is a member of the Scientific Advisory Board of VaxArt and Invivyd. R.S.B. has unrelated collaborations with J&J, Gilead, Ridgeback Biosciences, and Moderna.