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-Structure paper
| Title | Human monoclonal antibodies that target clade 2.3.4.4b H5N1 hemagglutinin. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2025 |
| Publish date | Dec 13, 2025 |
Authors | Garazi Peña Alzua / André Nicolás León / Temima Yellin / Disha Bhavsar / Madhumathi Loganathan / Kaitlyn Bushfield / Philip J M Brouwer / Alesandra J Rodriguez / Trushar Jeevan / Richard Webby / Christine Marizzi / Julianna Han / Andrew B Ward / J Andrew Duty / Florian Krammer / ![]() |
| PubMed Abstract | The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds, as well as in mammals, which ...The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds, as well as in mammals, which underscores its potential to cause a pandemic. Here, we generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. To develop human chimeric antibodies, H2L2 Harbor Mice®, which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007- original/2022 H5N1 virus. Through hybridoma technology, sixteen fully human mAbs are generated, most of which show cross-reactivity against H5 proteins from different clade 2.3.4.4 virus variants. Fourteen out of the sixteen mAbs neutralize the virus in vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrate greater neutralizing capacity and show increased protective effects in vivo when administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identify a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 during the coronavirus 2019 pandemic, these mAbs could serve as treatments in case of a widespread H5N1 epidemic or pandemic. |
External links | Nat Commun / PubMed:41390501 |
| Methods | EM (single particle) |
| Resolution | 3.06 - 25.0 Å |
| Structure data | EMDB-48510: Cryo-EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 20D10 and CR9114 EMDB-48511: Cryo-EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 12G1 and CR9114 EMDB-48512: Cryo-EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 6G1, 1A1 and CR9114 ![]() EMDB-48679: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 1A1 ![]() EMDB-48680: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 1H2 ![]() EMDB-48681: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 6G1 ![]() EMDB-48682: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 7G4 ![]() EMDB-48683: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 7G11 ![]() EMDB-48684: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 12C11 ![]() EMDB-48685: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 12G1 ![]() EMDB-48686: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 12G8 ![]() EMDB-48687: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 12G9 ![]() EMDB-48688: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 13E8 ![]() EMDB-48689: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 17C12 ![]() EMDB-48690: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 17E3 ![]() EMDB-48692: Negative stain EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fab 20D10 ![]() EMDB-48693: A/Red-tailed hawk/New York/NYCVH 22-8477/2022 H5 in complex with monoclonal fab 1A1 ![]() EMDB-48694: Negative stain map of A/Red-tailed hawk/New York/NYCVH 22-8477/2022 H5 in complex with monoclonal Fab 20D10 ![]() EMDB-48695: Negative stain map of A/Red-tailed hawk/New York/NYCVH 22-8477/2022 H5 in complex with monoclonal Fab 6G1 ![]() EMDB-48696: Negative stain map of A/Red-tailed hawk/New York/NYCVH 22-8477/2022 H5 in complex with monoclonal Fab 12G1 ![]() EMDB-48822: Cryo-EM map of H5 HA (A/Jiangsu/NJ210/2023) in complex with monoclonal fabs 1A1, 6G1, and CR9114. |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / influenza / hemaglutinin / antibody-antigen complex / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / hemagglutinin / H5 / monoclonal / complex / fab complex / viral fusion protein |
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homo sapiens (human)
influenza a virus
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