tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jul 1;16(1):5831.
doi: 10.1038/s41467-025-60232-3. Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses
Arne Matthys[SUP] 1 2 [/SUP], Jan Felix[SUP] 2 3 [/SUP], Joao Paulo Portela Catani[SUP] 1 2 [/SUP], Kenny Roose[SUP] 1 2 [/SUP], Wim Nerinckx[SUP] 1 2 [/SUP], Benthe Van Buyten[SUP] 1 2 [/SUP], Daria Fijalkowska[SUP] 1 2 [/SUP], Nico Callewaert[SUP] 1 2 [/SUP], Savvas N Savvides[SUP] 2 3 [/SUP], Xavier Saelens[SUP] 4 5 [/SUP]
Affiliations
Influenza B viruses are antigenically diverse and contribute significantly to the annual influenza burden. Here we report influenza B virus neutralizing single-domain antibodies that target highly conserved regions of the hemagglutinin and neuraminidase. Structural studies by single particle electron cryo-microscopy (cryo-EM) revealed that one of these single-domain antibodies prevents the conformational transition of the viral hemagglutinin to the post-fusion state by targeting a quaternary epitope spanning two protomers in the hemagglutinin-stem region. A second single-domain antibody broadly inhibits influenza B neuraminidase activity, including an oseltamivir-resistant neuraminidase, and its complex with neuraminidase elucidated by single particle cryo-EM established that it binds to residues in the neuraminidase catalytic site. Head-to-tail fusions of these single-domain antibodies led to bispecific binders that further improved the neutralization breadth and potency against influenza B viruses. These single-domain antibodies, fused to a human IgG1-Fc domain, fully protected female mice against an otherwise lethal influenza B virus challenge. Our findings underscore the potential of engineered single-domain antibodies to help control influenza B virus infections.
. 2025 Jul 1;16(1):5831.
doi: 10.1038/s41467-025-60232-3. Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses
Arne Matthys[SUP] 1 2 [/SUP], Jan Felix[SUP] 2 3 [/SUP], Joao Paulo Portela Catani[SUP] 1 2 [/SUP], Kenny Roose[SUP] 1 2 [/SUP], Wim Nerinckx[SUP] 1 2 [/SUP], Benthe Van Buyten[SUP] 1 2 [/SUP], Daria Fijalkowska[SUP] 1 2 [/SUP], Nico Callewaert[SUP] 1 2 [/SUP], Savvas N Savvides[SUP] 2 3 [/SUP], Xavier Saelens[SUP] 4 5 [/SUP]
Affiliations
- PMID: 40593518
- PMCID: PMC12217591
- DOI: 10.1038/s41467-025-60232-3
Influenza B viruses are antigenically diverse and contribute significantly to the annual influenza burden. Here we report influenza B virus neutralizing single-domain antibodies that target highly conserved regions of the hemagglutinin and neuraminidase. Structural studies by single particle electron cryo-microscopy (cryo-EM) revealed that one of these single-domain antibodies prevents the conformational transition of the viral hemagglutinin to the post-fusion state by targeting a quaternary epitope spanning two protomers in the hemagglutinin-stem region. A second single-domain antibody broadly inhibits influenza B neuraminidase activity, including an oseltamivir-resistant neuraminidase, and its complex with neuraminidase elucidated by single particle cryo-EM established that it binds to residues in the neuraminidase catalytic site. Head-to-tail fusions of these single-domain antibodies led to bispecific binders that further improved the neutralization breadth and potency against influenza B viruses. These single-domain antibodies, fused to a human IgG1-Fc domain, fully protected female mice against an otherwise lethal influenza B virus challenge. Our findings underscore the potential of engineered single-domain antibodies to help control influenza B virus infections.