Identification of a seasonal influenza vaccine–induced broadly protective neuraminidase antibody
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.
Authors
- Hanover Matz (ORCID: https://orcid.org/0000-0002-0669-1696)
- Tossapol Pholcharee (ORCID: https://orcid.org/0000-0002-5347-1936)
- Anders Madsen (ORCID: https://orcid.org/0000-0002-0626-5443)
- Ali H. Ellebedy (ORCID: https://orcid.org/0000-0002-6129-2532)
- Fangjie Han
- Nicholas C. Wu (ORCID: https://orcid.org/0000-0002-9078-6697)
- Julian Q. Zhou (ORCID: https://orcid.org/0000-0001-9602-2092)
- Sameer Kumar Malladi (ORCID: https://orcid.org/0000-0001-5131-4518)
- Stephen Horváth (ORCID: https://orcid.org/0000-0001-5324-1666)
- Aaron J. Schmitz (ORCID: https://orcid.org/0000-0002-8077-6751)
- Jackson S. Turner (ORCID: https://orcid.org/0000-0002-4396-6265)
- Nisreen M.A. Okba (ORCID: https://orcid.org/0000-0002-2394-1079)
- Florian Krammer (ORCID: https://orcid.org/0000-0003-4121-776X)
- Huibin Lv (ORCID: https://orcid.org/0000-0003-2218-0076)
- Maria Ibanez Trullen
Institutions
- Semmelweis University (HU)
- University of Illinois Urbana-Champaign (US)
- Illinois College (US)
- Washington University in St. Louis (US)
- Haukeland University Hospital (NO)
- University of Bergen (NO)
- Medical University of Vienna (AT)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-04-03
- DOI
- https://doi.org/10.1084/jem.20241930
- Citations
- 5
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 6.77
Funders
- Howard Hughes Medical Institute
- Purdue University
- Alvin J. Siteman Cancer Center
- Moderna
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- Division of Materials Research