Cell . Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

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Cell


. 2020 Sep 16;S0092-8674(20)31234-4.
doi: 10.1016/j.cell.2020.09.037. Online ahead of print.
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology


Luca Piccoli ¹ , Young-Jun Park ² , M Alejandra Tortorici ³ , Nadine Czudnochowski ⁴ , Alexandra C Walls ² , Martina Beltramello ¹ , Chiara Silacci-Fregni ¹ , Dora Pinto ¹ , Laura E Rosen ⁴ , John E Bowen ² , Oliver J Acton ² , Stefano Jaconi ¹ , Barbara Guarino ¹ , Andrea Minola ¹ , Fabrizia Zatta ¹ , Nicole Sprugasci ¹ , Jessica Bassi ¹ , Alessia Peter ¹ , Anna De Marco ¹ , Jay C Nix ⁵ , Federico Mele ⁶ , Sandra Jovic ⁶ , Blanca Fernandez Rodriguez ⁶ , Sneha V Gupta ⁴ , Feng Jin ⁴ , Giovanni Piumatti ⁷ , Giorgia Lo Presti ⁸ , Alessandra Franzetti Pellanda ⁸ , Maira Biggiogero ⁸ , Maciej Tarkowski ⁹ , Matteo S Pizzuto ¹ , Elisabetta Cameroni ¹ , Colin Havenar-Daughton ⁴ , Megan Smithey ⁴ , David Hong ⁴ , Valentino Lepori ¹⁰ , Emiliano Albanese ¹¹ , Alessandro Ceschi ¹² , Enos Bernasconi ¹³ , Luigia Elzi ¹⁴ , Paolo Ferrari ¹⁵ , Christian Garzoni ⁸ , Agostino Riva ⁹ , Gyorgy Snell ⁴ , Federica Sallusto ⁶ , Katja Fink ¹ , Herbert W Virgin ⁴ , Antonio Lanzavecchia ¹ , Davide Corti ¹⁶ , David Veesler ¹⁷



Affiliations

• PMID: 32991844
• PMCID: PMC7494283
• DOI: 10.1016/j.cell.2020.09.037

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; coronaviruses; effector functions; immunity; neutralizing antibodies.