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| Title | The N terminus of H3-influenza hemagglutinin as a site-of-vulnerability to neutralizing antibody. |
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| Journal, issue, pages | Structure, Vol. 33, Issue 11, Page 1820-11830.e4, Year 2025 |
| Publish date | Nov 6, 2025 |
Authors | Reda Rawi / Nicholas C Morano / Crystal Sao-Fong Cheung / Haijuan Du / Jason Gorman / Madhu Prabhakaran / Jordan E Becker / Tatsiana Bylund / Sam Charaf / Xuejun Chen / Myungjin Lee / Darcy R Harris / Adam S Olia / Li Ou / Lingshu Wang / Shuishu Wang / Baoshan Zhang / Masaru Kanekiyo / Adrian B McDermott / Tongqing Zhou / Lawrence Shapiro / Peter D Kwong / ![]() |
| PubMed Abstract | The N terminus of the H3 subtype of influenza virus hemagglutinin is ∼10 residues longer than the N termini of most other hemagglutinins. As conserved, exposed, and linear regions may be good ...The N terminus of the H3 subtype of influenza virus hemagglutinin is ∼10 residues longer than the N termini of most other hemagglutinins. As conserved, exposed, and linear regions may be good vaccine targets, we investigated the vaccine utility of the extended H3-N terminus. First, we identified antibody 5E10, for which structure and binding analyses revealed recognition of the H3-N terminus. Second, we immunized mice with immunogens incorporating the H3-N terminus, boosted with hemagglutinin trimer, and isolated antibodies from immunogen-elicited B cells that bound both H3-N terminus and hemagglutinin trimer. However, hemagglutinin-complex structures of two such antibodies, 3864-6 and 3864-10, that neutralized H3-influenza strains, revealed only peripheral recognition of the hemagglutinin N terminus. Collectively, these results reveal the N terminus of H3 hemagglutinin to be a suboptimal vaccine target and suggest that-in addition to being conserved, flexible, and accessible-other factors influence the elicitation of potent broadly neutralizing responses. |
External links | Structure / PubMed:40816277 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.83 - 3.89 Å |
| Structure data | EMDB-48078, PDB-9ei8: EMDB-48079, PDB-9ei9: |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | IMMUNE SYSTEM / HA / influenza / flu / N-term / H3 / sing16 |
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influenza a virus
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