Summary 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 (IC 50 < 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. Graphical abstract Highlights • Map 377 mAbs: 19 of 80 recognizing the RBD are potent neutralizers; 1 potent NTD binder • 19 Fab-antigen complex structures; 80 mAbs mapped on RBD and clustered into 5 epitopes • Most potent mAbs are ACE2 blockers, neutralize with few ACE2s, some Fabs glycosylated • mAbs reveal unique examples of NTD binding, RBD binding mode, and LC optimization Dejnirattisai et al. present an in-depth study of the human antibody response to SARS-CoV-2 infection. By characterizing 377 human mAbs from recovered COVID-19 patients, and determining 19 protein structures, they construct a map of antibody footprints on the RBD that describes in great detail its antigenic anatomy.
【저자키워드】 coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure, 【초록키워드】 neutralizing antibody, SARS-CoV-2, antibody, SARS-COV-2 infection, X-ray crystallography, animal models, Receptor binding domain, Protein, RBD, Microscopy, Human monoclonal antibody, Neutralizing, NTD, receptor, epitope, mAbs, binding, immune protection, mAb, Emergency use, Fab, N-terminal domain, Interaction, Recovered COVID-19 patients, structures, Abstract, human antibody response, complex, antigenic, RBD binding, MOST, inhibitory, Virus spike, Anatomy, data-driven, neutralize, bind, PROTECT, identify, example, unique, the RBD, recognizing, dissect, mapped, glycosylated, Map, ACE2 blockers, antibody binding site, binding mode, inhibitory antibody, panel of antibody, prophylactically, 【제목키워드】 SARS-CoV-2 receptor, antigenic, binding domain, Anatomy,