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| Title | Single-domain antibodies directed against hemagglutinin and neuraminidase protect against influenza B viruses. |
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| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 5831, Year 2025 |
| Publish date | Jul 1, 2025 |
Authors | Arne Matthys / Jan Felix / Joao Paulo Portela Catani / Kenny Roose / Wim Nerinckx / Benthe Van Buyten / Daria Fijalkowska / Nico Callewaert / Savvas N Savvides / Xavier Saelens / ![]() |
| PubMed Abstract | 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 ...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. |
External links | Nat Commun / PubMed:40593518 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.93 - 3.6 Å |
| Structure data | EMDB-50546, PDB-9fm1: EMDB-50547, PDB-9fm2: |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | ANTIVIRAL PROTEIN / hemagglutinin / single-domain antibody / complex / neuraminidase |
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