228: Two non-competing H3N2 stem antibodies reveal evolving antigenicity

️ Episode 228: Two non-competing H3N2 stem antibodies reveal evolving antigenicity In this episode of PaperCast Base by Base, we explore Structural and functional characterization of two group 2 H3 HA stem antibodies, 2F02 and AG2-G02, shows distinct non-overlapping epitopes, protection in mice, and antigenic changes driven by HA2 position 32 that limit AG2-G02 binding Study Highlights:Cryo-EM structures show 2F02 targets the central stem epitope while AG2-G02 targets the lower stem epitope and the two can bind concurrently to an HA trimer. Both antibodies neutralize diverse H3 strains in vitro and provide prophylactic protection in mice, with Fc-mediated effector functions contributing to in vivo efficacy. AG2-G02 binding is lost to recent human H3N2 HAs carrying R32 at HA2, whereas T32 or I32 permit binding. Human plasma binding profiles mirror the historical shift from T32 to I32 to R32, indicating altered population antigenicity of the lower stem over time. Conclusion:Natural evolution at HA2 position 32 has changed the antigenicity of the H3N2 HA lower stem, impacting binding of certain group 2 stem antibodies and informing vaccine design strategies Music:Enjoy the music based on this article at the end of the episode. Reference:Gopal AB, Lv H, Ouyang WO, Teo QW, Luo Y, Tang YS, Luo M, Mok CKP, Wu NC. Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity. Nat Commun. 2025;16:10557. https://doi.org/10.1038/s41467-025-65595-1 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com Castos player https://basebybase.castos.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

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