2025/03/07 by Anders Madsen, Nisreen M.A. Okba, Tossapol Pholcharee +12 · 2 voices · 1 citation
Medicine · Immunology and Microbiology · #Influenza Virus Research Studies #Respiratory viral infections research #Immune Cell Function and Interaction
paper · pdf · doi:10.1084/jem.20241930
openalex publication_date 2025/03/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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.