Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
By C. Barnes, A. West, Kathryn E Huey-Tubman, Magnus A. G. Hoffmann, N. G. Sharaf, Pauline R. Hoffman, Nicholas S Koranda, H. Gristick, C. Gaebler, Frauke Muecksch and 13 more. 2020
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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 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.
Subfields: Animal Science and Zoology, Infectious Diseases, Radiology, Nuclear Medicine and Imaging
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Citations in the corpus
- Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “In Kymab Darwin mice, the nanoparticle vaccines had lower (better) ratios than S-2P–immunized mice, but higher than HCS (Figure 6E).”
- Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition (2020, positive): “In addition, anti-RBD antibodies often dominate the neutralizing activity of the polyclonal antibody response elicited by natural infection (Barnes et al., 2020a; Steffen et al., 2020; Weisblum et al., 2020) .”
- SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma (2021, positive): “This dramatic effect on plasma neutralization can be explained by the dominance of RBD-directed neutralizing antibodies 10,11,13 .”
- Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, neutral): “peptide were previously described (47).”
- Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, positive): “Since RBD-directed responses that target the ACE-2 binding site form a dominant proportion of neutralizing immune responses in infected patients 36 , constructs that increase exposure and access to these sites could be useful candidates for vaccination regimens aimed at eliciting such responses.”
- Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “The S2A4 mAb was isolated from memory B cells The observation of SARS-CoV-2 S trimers with two and three RBDs open suggests that S2H14 binding conformationally selects open RBDs in a way reminiscent of the SARS-CoV S230 (Walls et al., 2019) and of the SARS-CoV-2 C105 (Barnes et al., 2020) neutralizi”
- A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “The neutralizing antibody response to SARS-CoV-2 is often focused on just a small portion of spike [36,61,72,73], and key receptor-binding loops are mutationally tolerant in the spikes of both 229E [25,53] and SARS-CoV-2 [74].”