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 S1A 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.
Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization
Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody.
Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.
Structural basis for potent cross-neutralizing human monoclonal antibody protection against lethal human and zoonotic severe acute respiratory syndrome coronavirus challenge
New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0
Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies.
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site
Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding
Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains
The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector
Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo.
Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.
The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies
A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody.
Suitability of two rapid lateral flow immunochromatographic assays for predicting SARS-CoV-2 neutralizing activity of sera.
The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies.
Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients.
Computational design of SARS-CoV-2 spike glycoproteins to increase immunogenicity by T cell epitope engineering
Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.
Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins.
High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post-HIV Env trimer vaccination.
Elucidation of interactions regulating conformational stability and dynamics of SARS-CoV-2 S-protein.
In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses.
Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection.
Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)
Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study.
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