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bioRxiv · 10.1101/2025.07.01.662631

Structural and functional characterization of the antigenicity of influenza A virus hemagglutinin subtype H15

Bhavsar, D.·Leon, A. N.·Hsu, W.-L.·Puente-Massaguer, E.·Ferguson, J.·Han, J.·Wilson, P.·Ward, A.·Krammer, F.
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Abstract

Avian H15 influenza viruses are closely related to H7 viruses, but feature a unique 9-amino acid insertion in their hemagglutinin head domain, creating an additional site for antigenic variation. Here, we characterized a panel of mouse monoclonal antibodies (mAbs) raised against the A/wedge-tailed shearwater/Western Australia/2576/1979 ancestral strain, and a human mAb isolated from an H7N9 vaccinee. We found differences in binding and neutralization profiles against the ancestral strain and drifted strains of H15 isolated after 2008. MAbs that have hemagglutination inhibition activity against the ancestral strain do not show binding to drifted strains, hinting at antigenic differences in the receptor binding site. We show that the mAbs protect in vivo and elucidate mAb-antigen interactions using negative stain and cryo-electron microscopy. The characterization of H15 antigenicity and mechanisms of antibody-mediated neutralization expands our knowledge of this rare avian influenza virus and informs our understanding of immune pressures on viral surface glycoproteins.

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Bhavsar, D., Leon, A. N., Hsu, W.-L., Puente-Massaguer, E., Ferguson, J., Han, J., Wilson, P., Ward, A., Krammer, F.. 2025-07-01. Structural and functional characterization of the antigenicity of influenza A virus hemagglutinin subtype H15. https://doi.org/10.1101/2025.07.01.662631

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