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TitleIdentification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody.
Journal, issue, pagesJ Exp Med, Vol. 222, Issue 6, Year 2025
Publish dateJun 2, 2025
AuthorsAnders Madsen / Nisreen M A Okba / Tossapol Pholcharee / Hanover C Matz / Huibin Lv / Maria Ibanez Trullen / Julian Q Zhou / Jackson S Turner / Aaron J Schmitz / Fangjie Han / Stephen C Horvath / Sameer Kumar Malladi / Florian Krammer / Nicholas C Wu / Ali H Ellebedy /
PubMed AbstractSeasonal influenza viruses cause significant global illness and death annually, and the potential spillover of avian H5N1 poses a serious pandemic threat. Traditional influenza vaccines target the ...Seasonal influenza viruses cause significant global illness and death annually, and the potential spillover of avian H5N1 poses a serious pandemic threat. Traditional influenza vaccines target the variable hemagglutinin (HA) protein, necessitating annual vaccine updates, while the slower-evolving neuraminidase (NA) presents a promising target for broader protection. We investigated the breadth of anti-NA B cell responses to seasonal influenza vaccination in humans. We screened plasmablast-derived monoclonal antibodies (mAbs) from three donors, identifying 11 clonally distinct NA mAbs from 268 vaccine-specific mAbs. Among these, mAb-297 showed exceptionally broad NA inhibition, effectively protecting mice against lethal doses of influenza A and B viruses, including H5N1. We show that mAb-297 targets a common binding motif in the conserved NA active site. Our findings show that while B cell responses against NA following conventional, egg-derived influenza vaccines are rare, inducing broadly protective NA antibodies through such vaccination remains feasible, highlighting the importance of improving NA immunogens to develop a more broadly protective influenza vaccine.
External linksJ Exp Med / PubMed:40178595 / PubMed Central
MethodsEM (single particle)
Resolution2.65 Å
Structure data

47102

9dpc

EMDB-47102, PDB-9dpc:
Structure of Fab 297 in complex with influenza H1N1 A/Victoria/4897/2022 neuraminidase
Method: EM (single particle) / Resolution: 2.65 Å

Source
  • homo sapiens (human)
  • influenza a virus
KeywordsIMMUNE SYSTEM / Influenza / Neuraminidase / Antibody

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