Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface

Xueyong Zhu, Julianna Han, Weina Sun, Eduard Puente-Massaguer, Wenli Yu, Peter Palese, Florian Krammer, Andrew B. Ward, Ian A. Wilson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of generating universal influenza immunity. Two group 2 influenza A chimeric HAs, cH4/3 and cH15/3, were previously designed to elicit antibodies to the conserved HA stem. Here, we show by X-ray crystallography and negative-stain electron microscopy that a broadly protective antistem antibody can stably bind to cH4/3 and cH15/3 HAs, thereby validating their potential as universal vaccine immunogens. Furthermore, flexibility was observed in the head domain of the chimeric HA structures, suggesting that antibodies could also potentially interact with the head interface epitope. Our structural and binding studies demonstrated that a broadly protective antihead trimeric interface antibody could indeed target the more open head domain of the cH15/3 HA trimer. Thus, in addition to inducing broadly protective antibodies against the conserved HA stem, chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain, thereby increasing the vaccine efficacy.

Original languageEnglish
Article numbere2200821119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - 24 May 2022


  • HA trimer interface
  • X-ray crystallography
  • chimeric influenza hemagglutinin
  • negative-stain electron microscopy
  • stem
  • universal vaccine design


Dive into the research topics of 'Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface'. Together they form a unique fingerprint.

Cite this