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

被引：994

作者：

Piccoli, Luca ^{[1
]}

Park, Young-Jun ^{[2
]}

Tortorici, M. Alejandra ^{[2
,3
,4
]}

Czudnochowski, Nadine ^{[5
]}

Walls, Alexandra C. ^{[2
]}

Beltramello, Martina ^{[1
]}

Silacci-Fregni, Chiara ^{[1
]}

Pinto, Dora ^{[1
]}

Rosen, Laura E. ^{[5
]}

Bowen, John E. ^{[2
]}

Acton, Oliver J. ^{[2
]}

Jaconi, Stefano ^{[1
]}

Guarino, Barbara ^{[1
]}

Minola, Andrea ^{[1
]}

Zatta, Fabrizia ^{[1
]}

Sprugasci, Nicole ^{[1
]}

Bassi, Jessica ^{[1
]}

Peter, Alessia ^{[1
]}

De Marco, Anna ^{[1
]}

Nix, Jay C. ^{[6
]}

Mele, Federico ^{[7
]}

Jovic, Sandra ^{[7
]}

Rodriguez, Blanca Fernandez ^{[7
]}

Gupta, Sneha, V ^{[5
]}

Jin, Feng ^{[5
]}

Piumatti, Giovanni ^{[8
,9
]}

Lo Presti, Giorgia ^{[10
]}

Pellanda, Alessandra Franzetti ^{[10
]}

Biggiogero, Maira ^{[10
]}

Tarkowski, Maciej ^{[11
]}

Pizzuto, Matteo S. ^{[1
]}

Cameroni, Elisabetta ^{[1
]}

Havenar-Daughton, Colin ^{[5
]}

Smithey, Megan ^{[5
]}

Hong, David ^{[5
]}

Lepori, Valentino

Albanese, Emiliano ^{[12
]}

Ceschi, Alessandro ^{[9
,13
,14
]}

Bernasconi, Enos ^{[15
,16
]}

Elzi, Luigia ^{[17
,18
]}

Ferrari, Paolo ^{[19
,20
]}

Garzoni, Christian ^{[10
]}

Riva, Agostino ^{[11
]}

Snell, Gyorgy ^{[5
]}

Sallusto, Federica ^{[7
]}

Fink, Katja ^{[1
]}

Virgin, Herbert W. ^{[5
]}

Lanzavecchia, Antonio ^{[1
]}

Corti, Davide ^{[1
]}

Veesler, David ^{[2
]}

机构：

[1] Humabs BioMed SA, Vir Biotechnol, CH-6500 Bellinzona, Switzerland

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Inst Pasteur, F-75015 Paris, France

[4] CNRS UMR 3569, Unite Virol Structurale, F-75015 Paris, France

[5] Vir Biotechnol, San Francisco, CA 94158 USA

[6] Lawrence Berkeley Natl Lab, Adv Light Source, Mol Biol Consortium, Berkeley, CA 94720 USA

[7] Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[8] Geneva Univ Hosp, Div Primary Care, CH-1205 Geneva, Switzerland

[9] Univ Svizzera Italiana, Fac Biomed Sci, CH-6900 Lugano, Switzerland

[10] Clin Luganese Moncucco, Clin Internal Med & Infect Dis, CH-6900 Lugano, Switzerland

[11] Luigi Sacco Hosp, Div Infect Dis 3, ASST Fatebenefratelli Sacco, I-20157 Milan, Italy

[12] Univ Svizzera Italiana, Inst Publ Hlth, CH-6900 Lugano, Switzerland

[13] Ente Osped Cantonale, Div Clin Pharmacol & Toxicol, Inst Pharmacol Sci Southern Switzerland, CH-6900 Lugano, Switzerland

[14] Univ Hosp Zurich, Dept Clin Pharmacol & Toxicol, CH-8091 Zurich, Switzerland

[15] Ente Osped Cantonale, Osped Civ, Div Infect Dis, CH-6900 Lugano, Switzerland

[16] Osped Italiano, CH-6900 Lugano, Switzerland

[17] Osped Reg Bellinzona & Valli, Div Infect Dis, Ente Osped Cantonale, CH-6600 Locarno, Switzerland

[18] Osped Reg, CH-6600 Locarno, Switzerland

[19] Ente Osped Cantonale, Osped Civ Lugano, Dept Nephrol, CH-6900 Lugano, Switzerland

[20] Univ New South Wales, Prince Wales Hosp, Clin Sch, Sydney, NSW 2052, Australia

来源：

CELL | 2020年 / 183卷 / 04期

基金：

美国国家卫生研究院;

关键词：

HUMAN MONOCLONAL-ANTIBODY; CRYO-EM STRUCTURE; FC-RECEPTOR; BAYESIAN-APPROACH; HUMORAL IMMUNITY; MERS-COV; B-CELLS; CORONAVIRUS; VIRUS; VALIDATION;

D O I：

10.1016/j.cell.2020.09.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 647SARS-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 overtime for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serumAbs 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.

引用

页码：1024 / +

页数：40

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