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-Structure paper
Title | Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes. |
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Journal, issue, pages | Immunity, Vol. 55, Issue 12, Page 2419-2435.e10, Year 2022 |
Publish date | Dec 13, 2022 |
Authors | Chengcheng Fan / Alexander A Cohen / Miso Park / Alfur Fu-Hsin Hung / Jennifer R Keeffe / Priyanthi N P Gnanapragasam / Yu E Lee / Han Gao / Leesa M Kakutani / Ziyan Wu / Harry Kleanthous / Kathryn E Malecek / John C Williams / Pamela J Bjorkman / |
PubMed Abstract | Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding ...Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs. |
External links | Immunity / PubMed:36370711 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.2 - 4.1 Å |
Structure data | EMDB-26878, PDB-7uz4: EMDB-26879, PDB-7uz5: EMDB-26880, PDB-7uz6: EMDB-26881, PDB-7uz7: EMDB-26882, PDB-7uz8: EMDB-26883, PDB-7uz9: EMDB-26884, PDB-7uza: EMDB-26885, PDB-7uzb: PDB-7uzc: PDB-7uzd: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
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Keywords | IMMUNE SYSTEM/VIRAL PROTEIN / immune system / neutralizing antibody / IMMUNE SYSTEM-VIRAL PROTEIN complex |