Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41298395.
- Also identified by DOI 10.1038/s41467-025-65595-1 and PMC identifier 12658140.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The conserved stem domain of influenza hemagglutinin (HA), which is classified into group 1 and group 2, is a target of broadly neutralizing antibodies. While many group 1 HA stem antibodies have been described, much less is known about group 2 HA stem antibodies. This study structurally characterizes two group 2 HA stem antibodies, 2F02 and AG2-G02, targeting the central stem epitope and the lower stem epitope, respectively. Unlike prototypic antibodies to group 2 HA stem, 2F02 and AG2-G02 do not compete for binding. Both antibodies offer protection in a female mouse model via neutralization activity and Fc-mediated effector functions. We further demonstrate that the natural evolution of HA2 position 32 restricts the binding of AG2-G02 to recent human H3N2 HAs and influences the binding of human plasma samples. Overall, these findings advance our understanding of the antigenicity of HA stem, which has important implications for the development of broadly protective influenza vaccines.
Medical subject headings
- Hemagglutinin Glycoproteins, Influenza Virus
- Influenza A Virus, H3N2 Subtype
- Antibodies, Viral
- Antigens, Viral