Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

被引：163

作者：

Andreano, Emanuele ^{[1
]}

Nicastri, Emanuele ^{[4
]}

Paciello, Ida ^{[1
]}

Pileri, Piero ^{[1
]}

Manganaro, Noemi ^{[1
]}

Piccini, Giulia ^{[2
]}

Manenti, Alessandro ^{[2
,3
]}

Pantano, Elisa ^{[1
]}

Kabanova, Anna ^{[1
,11
]}

Troisi, Marco ^{[1
,9
]}

Vacca, Fabiola ^{[1
,9
]}

Cardamone, Dario ^{[1
,10
]}

De Santi, Concetta ^{[1
]}

Torres, Jonathan L. ^{[17
]}

Ozorowski, Gabriel ^{[17
]}

Benincasa, Linda ^{[3
]}

Jang, Hyesun ^{[14
]}

Di Genova, Cecilia ^{[16
]}

Depau, Lorenzo ^{[12
,13
]}

Brunetti, Jlenia ^{[12
,13
]}

Agrati, Chiara ^{[4
]}

Capobianchi, Maria Rosaria ^{[4
]}

Castilletti, Concetta ^{[4
]}

Emiliozzi, Arianna ^{[5
,6
]}

Fabbiani, Massimiliano ^{[6
]}

Montagnani, Francesca ^{[5
,6
]}

Bracci, Luisa ^{[12
,13
]}

Sautto, Giuseppe ^{[14
]}

Ross, Ted M. ^{[14
,15
]}

Montomoli, Emanuele ^{[2
,3
,7
]}

Temperton, Nigel ^{[16
]}

Ward, Andrew B. ^{[17
]}

Sala, Claudia ^{[1
]}

Ippolito, Giuseppe ^{[4
]}

Rappuoli, Rino ^{[1
,8
]}

机构：

[1] Fdn Toscana Life Sci, Monoclonal Antibody Discovery MAD Lab, Siena, Italy

[2] VisMederi Srl, Siena, Italy

[3] VisMederi Res Srl, Siena, Italy

[4] IRCCS, Natl Inst Infect Dis Lazzaro Spallanzani, Rome, Italy

[5] Univ Siena, Dept Med Biotechnol, Siena, Italy

[6] Univ Hosp Siena, Dept Med Sci, Infect & Trop Dis Unit, Siena, Italy

[7] Univ Siena, Dept Mol & Dev Med, Siena, Italy

[8] Imperial Coll, Fac Med, London, England

[9] Univ Siena, Dept Biotechnol Chem & Pharm, Siena, Italy

[10] Univ Turin, Turin, Italy

[11] Fdn Toscana Life Sci, Tumour Immunol Unit, Siena, Italy

[12] Univ Siena, MedBiotech Hub, Dept Med Biotechnol, Siena, Italy

[13] Univ Siena, Competence Ctr, Dept Med Biotechnol, Siena, Italy

[14] Univ Georgia, Ctr Vaccines & Immunol, Athens, GA 30602 USA

[15] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA

[16] Univ Kent, Medway Sch Pharm, Viral Pseudotype Unit, Chatham, Kent, England

[17] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

来源：

CELL | 2021年 / 184卷 / 07期

基金：

欧盟地平线“2020”; 英国惠康基金; 欧洲研究理事会;

关键词：

CRYO-EM STRUCTURE; CELLS; SPIKE;

D O I：

10.1016/j.cell.2021.02.035

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：

Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.

引用

页码：1821 / +

页数：31

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