Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology
By L. Piccoli, Young-Jun Park, ... M. Alejandra Tortorici, Antonio Lanzavecchia, Davide Corti, D. Veesler, M. A. Tortorici, N. Czudnochowski, A. Walls, M. Beltramello and 41 more. 2020
317 citations recorded by the source corpus.
Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.
Subfields: Animal Science and Zoology, Infectious Diseases
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Citations in the corpus
- Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “Several recent studies have indicated that the RBD is the target of most neutralizing activity in COVID-19 HCS (Barnes et al., 2020; Brouwer et al., 2020; Piccoli et al., 2020; Pinto et al., 2020; Robbiani et al., 2020; Seydoux et al., 2020; Wang et al., 2020a; Wu et al., 2020).”
- Structural Analysis of the SARS-CoV-2 Omicron Variant Proteins (2021, unknown): “The Omicron S1 RBD structure showed high similarities with the experimental structures (PDB: 6M17 and 6M0J) (Figures 1(d) and 1(e)), and the comparison of Omicron S1 RBD with experimental structures (PDB: 6M17[5], 6M0J [6], 6LZG [7], and 7JX3 [8]) showed low RMSD values (Figure 1(f)), which reflecte”
- Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, unknown): “The emergence of mutations at E484K in South African strains is concerning, because this change can impact the neutralizing activity of many RBD-specific mAbs and immune serum generated from convalescent subjects (Avanzato et al., 2020; Greaney et al., 2021; Liu et al., 2020b; Oude Munnink et al., 2”
- Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, unknown): “Spike is the target of SARS-CoV-2 neutralizing antibodies, and the receptor binding domain (RBD) of Spike is the target of >90% of neutralizing antibodies in COVID-19 cases (Brouwer et al., 2020; Piccoli et al., 2020; Robbiani et al., 2020; Rogers et al., 2020; Suthar et al., 2020), with some neutra”