Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity
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.
Authors
- Mingyong Luo (ORCID: https://orcid.org/0000-0002-1202-1429)
- Tossapol Pholcharee (ORCID: https://orcid.org/0000-0002-5347-1936)
- Nicholas C. Wu (ORCID: https://orcid.org/0000-0002-9078-6697)
- Wenhao O. Ouyang (ORCID: https://orcid.org/0000-0002-3618-9808)
- Qi Wen Teo (ORCID: https://orcid.org/0000-0001-6749-9684)
- Chris Ka Pun Mok (ORCID: https://orcid.org/0000-0002-0525-6772)
- Akshita B. Gopal (ORCID: https://orcid.org/0000-0002-6429-0073)
- Yasha Luo (ORCID: https://orcid.org/0000-0002-2690-0221)
- Yun Sang Tang (ORCID: https://orcid.org/0000-0002-4873-8712)
- Huibin Lv (ORCID: https://orcid.org/0000-0003-2218-0076)
Institutions
- University of Illinois Urbana-Champaign (US)
- Illinois College (US)
- Chinese University of Hong Kong (HK)
- Hong Kong Jockey Club (HK)
- Guangdong Province Women and Children Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1038/s41467-025-65595-1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Purdue University
- Searle Scholars Program
- University of Illinois at Urbana-Champaign
- Health and Medical Research Fund
- Division of Materials Research
- Carl R. Woese Institute for Genomic Biology