Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite

Structure. 2022 Jul 7;30(7):993-1003.e6. doi: 10.1016/j.str.2022.04.003. Epub 2022 Apr 29.


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.

Keywords: antibody class; hemagglutinin; influenza; neutralizing antibodies; stem supersite.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Hemagglutinins
  • Humans
  • Influenza A Virus, H7N9 Subtype* / metabolism
  • Influenza Vaccines*
  • Influenza, Human*


  • Antibodies, Neutralizing
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Influenza Vaccines