The antigenic anatomy of SARS-CoV-2 receptor binding domain.

Dejnirattisai W., Zhou D., Ginn HM., Duyvesteyn HME., Supasa P., Case JB., Zhao Y., Walter TS., Mentzer AJ., Liu C., Wang B., Paesen GC., Slon-Campos J., López-Camacho C., Kafai NM., Bailey AL., Chen RE., Ying B., Thompson C., Bolton J., Fyfe A., Gupta S., Tan TK., Gilbert-Jaramillo J., James W., Knight M., Carroll MW., Skelly D., Dold C., Peng Y., Levin R., Dong T., Pollard AJ., Knight JC., Klenerman P., Temperton N., Hall DR., Williams MA., Paterson NG., Bertram FKR., Siebert CA., Clare DK., Howe A., Radecke J., Song Y., Townsend AR., Huang K-YA., Fry EE., Mongkolsapaya J., Diamond MS., Ren J., Stuart DI., Screaton GR.

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

DOI

10.1016/j.cell.2021.02.032

Type

Journal article

Journal

Cell

Publication Date

15/04/2021

Volume

184

Pages

2183 - 2200.e22

Keywords

coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, Antibody, CHO Cells, COVID-19, Chlorocebus aethiops, Cricetulus, Epitopes, Female, HEK293 Cells, Humans, Male, Mice, Mice, Transgenic, Models, Molecular, Protein Binding, Protein Structure, Tertiary, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vero Cells

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