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TitleStructural and functional characterization of the antigenicity of influenza A virus hemagglutinin subtype H15.
Journal, issue, pagesCell Rep, Vol. 45, Issue 1, Page 116773, Year 2026
Publish dateJan 27, 2026
AuthorsDisha Bhavsar / André Nicolás León / Wei-Li Hsu / Eduard Puente-Massaguer / James A Ferguson / Julianna Han / Patrick Wilson / Andrew B Ward / Florian Krammer /
PubMed AbstractAvian H15 influenza viruses are closely related to H7 viruses, but only 22 H15 sequences have been reported since 1987, suggesting both rarity and minimal antigenic variation. Here, we characterized ...Avian H15 influenza viruses are closely related to H7 viruses, but only 22 H15 sequences have been reported since 1987, suggesting both rarity and minimal 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 exhibiting hemagglutination inhibition activity against the ancestral strain do not show binding to drifted strains, hinting at antigenic differences near 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 the mechanisms of antibody-mediated neutralization expands our knowledge of this sparsely sampled avian influenza virus subtype and informs our understanding of immune pressures on viral surface glycoproteins.
External linksCell Rep / PubMed:41485218 / PubMed Central
MethodsEM (single particle)
Resolution3.14 - 25.0 Å
Structure data

71419

9p9q

EMDB-71419, PDB-9p9q:
KL-H15-3G11 Fab in complex with soluble A/wedge-tailed shearwater/Western Australia/2576/1979 H15 hemagglutinin trimer
Method: EM (single particle) / Resolution: 3.7 Å

71420

9p9r

EMDB-71420, PDB-9p9r:
KL-H15-6H4 Fab in complex with soluble A/wedge-tailed shearwater/Western Australia/2576/1979 H15 hemagglutinin trimer
Method: EM (single particle) / Resolution: 3.14 Å

71421

9p9s

EMDB-71421, PDB-9p9s:
KL-H15-6G8 Fab in complex with soluble A/wedge-tailed shearwater/Western Australia/2576/1979 H15 hemagglutinin trimer
Method: EM (single particle) / Resolution: 3.41 Å

71422

9p9t

EMDB-71422, PDB-9p9t:
07-5G01 Fab in complex with soluble A/wedge-tailed shearwater/Western Australia/2576/1979 H15 hemagglutinin trimer
Method: EM (single particle) / Resolution: 3.33 Å

EMDB-71424: KL-H15-6F6 Fab in complex with soluble A/wedge-tailed shearwater/Western Australia/2576/1979 H15 hemagglutinin trimer
Method: EM (single particle) / Resolution: 3.34 Å

EMDB-71480: Negative stain map of H15 HA (A/wedge-tailed shearwater/Western Australia/2576/1979) in complex with monoclonal Fab 6G8
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-71481: Negative stain map of H15 HA (A/wedge-tailed shearwater/Western Australia/2576/1979) in complex with monoclonal Fab 3G11
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-71482: Negative stain map of H15 HA (A/wedge-tailed shearwater/Western Australia/2576/1979) in complex with monoclonal Fab 6F6
Method: EM (single particle) / Resolution: 25.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • influenza a virus (a/shearwater/west australia/2576/79(h15n9))
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN/Immune System / influenza virus / hemagglutinin / avian influenza virus / antibody Fab complex / glycoprotein / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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