tetano
Editor, Senior Moderator
J Exp Med
. 2025 Jun 2;222(6):e20241930.
doi: 10.1084/jem.20241930. Epub 2025 Apr 3. Identification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody
Anders Madsen[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nisreen M A Okba[SUP] #[/SUP][SUP] 4 5 [/SUP], Tossapol Pholcharee[SUP] #[/SUP][SUP] 6 [/SUP], Hanover C Matz[SUP] 3 [/SUP], Huibin Lv[SUP] 6 7 [/SUP], Maria Ibanez Trullen[SUP] 4 5 [/SUP], Julian Q Zhou[SUP] 3 [/SUP], Jackson S Turner[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 3 [/SUP], Fangjie Han[SUP] 3 [/SUP], Stephen C Horvath[SUP] 3 [/SUP], Sameer Kumar Malladi[SUP] 3 [/SUP], Florian Krammer[SUP] 4 5 8 9 [/SUP], Nicholas C Wu[SUP] 6 7 10 11 [/SUP], Ali H Ellebedy[SUP] 3 12 13 [/SUP]
Affiliations
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.
. 2025 Jun 2;222(6):e20241930.
doi: 10.1084/jem.20241930. Epub 2025 Apr 3. Identification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody
Anders Madsen[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nisreen M A Okba[SUP] #[/SUP][SUP] 4 5 [/SUP], Tossapol Pholcharee[SUP] #[/SUP][SUP] 6 [/SUP], Hanover C Matz[SUP] 3 [/SUP], Huibin Lv[SUP] 6 7 [/SUP], Maria Ibanez Trullen[SUP] 4 5 [/SUP], Julian Q Zhou[SUP] 3 [/SUP], Jackson S Turner[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 3 [/SUP], Fangjie Han[SUP] 3 [/SUP], Stephen C Horvath[SUP] 3 [/SUP], Sameer Kumar Malladi[SUP] 3 [/SUP], Florian Krammer[SUP] 4 5 8 9 [/SUP], Nicholas C Wu[SUP] 6 7 10 11 [/SUP], Ali H Ellebedy[SUP] 3 12 13 [/SUP]
Affiliations
- PMID: 40178595
- DOI: 10.1084/jem.20241930
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.