Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.
antibody class
hemagglutinin
influenza
neutralizing antibodies
stem supersite
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
07 07 2022
07 07 2022
Historique:
received:
29
06
2021
revised:
18
01
2022
accepted:
04
04
2022
pubmed:
1
5
2022
medline:
14
7
2022
entrez:
30
4
2022
Statut:
ppublish
Résumé
Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite.
Identifiants
pubmed: 35489332
pii: S0969-2126(22)00130-7
doi: 10.1016/j.str.2022.04.003
pmc: PMC9271601
mid: NIHMS1801616
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Hemagglutinins
0
Influenza Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
993-1003.e6Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103310
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AI005022
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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