National Academy of Sciences, Proceedings of the National Academy of Sciences, 21(119), 2022
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Significance Sequential vaccination with chimeric hemagglutinins (cHAs) that contain the same stem, but different head domains, can direct the antibody immune response to the conserved stem region. Structural information on cHAs is limited to one example containing a group 1 stem. Here, X-ray and electron microscopy structures revealed that cHAs cH4/3 and cH15/3, which contain a group 2 stem, with broadly protective stem antibody 31.a.83, have intact, native-like stem regions. Furthermore, the cHA head domains were in an open conformation, which exposes the conserved trimer interface region. Structure determination of cH15/3 HA with 31.a.83 and head interface antibody FluA-20 suggests that broadly protective antibodies could be elicited against both the conserved HA stem and the head interface.