Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity
Year: 2025
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Howard Hughes Medical Institute, Kinship Foundation, Purdue University, Vallee Foundation, University of Illinois System, Searle Scholars Program, Research Grants Council, University Grants Committee, Food and Health Bureau, University of Illinois at Urbana-Champaign, Health and Medical Research Fund, Division of Materials Research, Carl R. Woese Institute for Genomic Biology
OpenAlex ID: W4416719160