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TitleStructure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.
Journal, issue, pagesStructure, Vol. 30, Issue 7, Page 993-1003.e6, Year 2022
Publish dateApr 19, 2022
AuthorsCrystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting Teng / Raffaello Verardi / Shuishu Wang / Yongping Yang / Gwo-Yu Chuang / Adrian B McDermott / Tongqing Zhou / Peter D Kwong /
PubMed AbstractSeveral 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, ...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.
External linksStructure / PubMed:35489332 / PubMed Central
MethodsEM (single particle)
Resolution2.76 Å
Structure data

21961

6wxl

EMDB-21961, PDB-6wxl:
Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer
Method: EM (single particle) / Resolution: 2.76 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • Influenza A virus
  • homo sapiens (human)
  • influenza a virus (a/shanghai/js01/2013(h7n9))
KeywordsIMMUNE SYSTEM / VRC / VRC315 / Group 2 / Fab

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