9DPC

Structure of Fab 297 in complex with influenza H1N1 A/Victoria/4897/2022 neuraminidase

Summary for 9DPC

• Entry DOI: 10.2210/pdb9dpc/pdb
• EMDB information: 47102
• Descriptor: Neuraminidase, Variable domain of the heavy chain of Fab 297, Variable domain of the light chain of Fab 297 (3 entities in total)
• Functional Keywords: influenza, neuraminidase, antibody, immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 6
• Total formula weight: 232124.49

Authors

Pholcharee, T.,Wu, N.C. (deposition date: 2024-09-20, release date: 2025-03-19, Last modification date: 2025-05-14)

Primary citation

Madsen, A.,Okba, N.M.A.,Pholcharee, T.,Matz, H.C.,Lv, H.,Ibanez Trullen, M.,Zhou, J.Q.,Turner, J.S.,Schmitz, A.J.,Han, F.,Horvath, S.C.,Malladi, S.K.,Krammer, F.,Wu, N.C.,Ellebedy, A.H.
Identification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody.
J.Exp.Med., 222:-, 2025

PubMed Abstract: 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.

PubMed: 40178595
DOI: 10.1084/jem.20241930

Experimental method

ELECTRON MICROSCOPY (2.65 Å)