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TitleDiscovery and characterization of a pan-betacoronavirus S2-binding antibody.
Journal, issue, pagesStructure, Vol. 32, Issue 11, Page 1893-1909.e11, Year 2024
Publish dateNov 7, 2024
AuthorsNicole V Johnson / Steven C Wall / Kevin J Kramer / Clinton M Holt / Sivakumar Periasamy / Simone I Richardson / Nelia P Manamela / Naveenchandra Suryadevara / Emanuele Andreano / Ida Paciello / Giulio Pierleoni / Giulia Piccini / Ying Huang / Pan Ge / James D Allen / Naoko Uno / Andrea R Shiakolas / Kelsey A Pilewski / Rachel S Nargi / Rachel E Sutton / Alexandria A Abu-Shmais / Robert Parks / Barton F Haynes / Robert H Carnahan / James E Crowe / Emanuele Montomoli / Rino Rappuoli / Alexander Bukreyev / Ted M Ross / Giuseppe A Sautto / Jason S McLellan / Ivelin S Georgiev /
PubMed AbstractThe continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell ...The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
External linksStructure / PubMed:39326419 / PubMed Central
MethodsEM (single particle)
Resolution3.0 Å
Structure data

43139

8vcr

EMDB-43139, PDB-8vcr:
SARS-CoV-2 Spike S2 bound to Fab 54043-5
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 spike / S2 subunit / viral fusion / monoclonal antibody

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