Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability.
COVID-19
S2-directed antibody
SARS-CoV-2
beta-coronavirus
broadly neutralizing antibody
crystal structure
vaccine design
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
25
01
2022
revised:
06
05
2022
accepted:
21
06
2022
pubmed:
17
7
2022
medline:
9
9
2022
entrez:
16
7
2022
Statut:
ppublish
Résumé
Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 Å resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.
Identifiants
pubmed: 35841885
pii: S0969-2126(22)00235-0
doi: 10.1016/j.str.2022.06.004
pmc: PMC9284671
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Spike Glycoprotein, Coronavirus
0
Vaccines
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1233-1244.e7Commentaires et corrections
Type : UpdateOf
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interest.
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