Summary Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1 A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies. Graphical Abstract Highlights • COVID-19 plasma IgGs can recognize SARS-2, SARS, and MERS S proteins • EM reconstructions of polyclonal Fab-S complexes revealed S1 A and RBD epitopes • 3.4 Å cryo-EM structure of a neutralizing Fab-S complex showed binding to “up” RBDs • Structures define a recurrent VH3-53 / VH3-66 -derived anti-SARS-CoV-2 antibody class Analysis of plasma from recovering COVID-19 patients identifies common features of antibodies that determine protection.
【저자키워드】 COVID-19, convalescent plasma, SARS-CoV-2, IgG, coronavirus, SARS-CoV, MERS-CoV, ELISA, electron microscopy, Fab, 【초록키워드】 viruses, Structure, antibodies, S protein, antibody, Antibody Response, mutations, Cryo-electron microscopy, MERS, specificity, Epitopes, Immunoglobulin, anti-SARS-CoV-2 antibody, RBD, Microscopy, modeling, plasma, Neutralizing, cryo-EM, epitope, VH3-53, monoclonal, binding, SARS-CoV-2 spike, similarity, COVID-19 patient, criteria, spikes, complex, IgGs, trimeric spike, Fabs, crosslinking, plasma IgG, block, cryo-EM structure, feature, polyclonal, ACE2 receptor binding, convalescent individual, identify, affected, examined, characterized, coronavirus, determine, recognize, suggested, the receptor-binding domain, complexes, alpha- and beta-coronaviruses, VH3-30, VH3-66, 【제목키워드】 Structure, spike, Human, Recurrent, common, Bound,