tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 May 24;119(21):e2200821119.
doi: 10.1073/pnas.2200821119. Epub 2022 May 20.
Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface
Xueyong Zhu[SUP] 1 [/SUP], Julianna Han[SUP] 1 [/SUP], Weina Sun[SUP] 2 [/SUP], Eduard Puente-Massaguer[SUP] 2 [/SUP], Wenli Yu[SUP] 1 [/SUP], Peter Palese[SUP] 2 3 [/SUP], Florian Krammer[SUP] 2 4 [/SUP], Andrew B Ward[SUP] 1 [/SUP], Ian A Wilson[SUP] 1 5 [/SUP]
Affiliations
Abstract
SignificanceSequential 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.
Keywords: HA trimer interface and stem; X-ray crystallography; chimeric influenza hemagglutinin; negative-stain electron microscopy; universal vaccine design.
. 2022 May 24;119(21):e2200821119.
doi: 10.1073/pnas.2200821119. Epub 2022 May 20.
Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface
Xueyong Zhu[SUP] 1 [/SUP], Julianna Han[SUP] 1 [/SUP], Weina Sun[SUP] 2 [/SUP], Eduard Puente-Massaguer[SUP] 2 [/SUP], Wenli Yu[SUP] 1 [/SUP], Peter Palese[SUP] 2 3 [/SUP], Florian Krammer[SUP] 2 4 [/SUP], Andrew B Ward[SUP] 1 [/SUP], Ian A Wilson[SUP] 1 5 [/SUP]
Affiliations
- PMID: 35594401
- DOI: 10.1073/pnas.2200821119
Abstract
SignificanceSequential 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.
Keywords: HA trimer interface and stem; X-ray crystallography; chimeric influenza hemagglutinin; negative-stain electron microscopy; universal vaccine design.