Медицинская библиотека · Cell · 2020

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

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: Piccoli Luca, Park Young-Jun, Tortorici M Alejandra, Czudnochowski Nadine, Walls Alexandra C, Beltramello Martina, Silacci-Fregni Chiara, Pinto Dora, Rosen Laura E, Bowen John E, Acton Oliver J, Jaconi Stefano, Guarino Barbara, Minola Andrea, Zatta Fabrizia, Sprugasci Nicole, Bassi Jessica, Peter Alessia, De Marco Anna, Nix Jay C, Mele Federico, Jovic Sandra, Rodriguez Blanca Fernandez, Gupta Sneha V, Jin Feng, Piumatti Giovanni, Lo Presti Giorgia, Pellanda Alessandra Franzetti, Biggiogero Maira, Tarkowski Maciej, Pizzuto Matteo S, Cameroni Elisabetta, Havenar-Daughton Colin, Smithey Megan, Hong David, Lepori Valentino, Albanese Emiliano, Ceschi Alessandro, Bernasconi Enos, Elzi Luigia, Ferrari Paolo, Garzoni Christian, Riva Agostino, Snell Gyorgy, Sallusto Federica, Fink Katja, Virgin Herbert W, Lanzavecchia Antonio, Corti Davide, Veesler David. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology.. Cell. 2020. DOI: 10.1016/j.cell.2020.09.037.

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