Extremely potent human monoclonal antibodies from COVID-19 convalescent patients.

Extremely potent human monoclonal antibodies from COVID-19 convalescent patients.
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DOI:
10.1016/j.cell.2021.02.035
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发表时间:
2021-04-01
期刊:
影响因子:
64.5
通讯作者:
Rappuoli R
Rappuoli R
中科院分区:
生物学1区
文献类型:
--
作者:
Andreano E;Nicastri E;Paciello I;Pileri P;Manganaro N;Piccini G;Manenti A;Pantano E;Kabanova A;Troisi M;Vacca F;Cardamone D;De Santi C;Torres JL;Ozorowski G;Benincasa L;Jang H;Di Genova C;Depau L;Brunetti J;Agrati C;Capobianchi MR;Castilletti C;Emiliozzi A;Fabbiani M;Montagnani F;Bracci L;Sautto G;Ross TM;Montomoli E;Temperton N;Ward AB;Sala C;Ippolito G;Rappuoli R

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人类单克隆抗体是安全、预防和治疗的工具,可以快速开发,以帮助恢复2019年冠状病毒病(COVID-19)大流行造成的大规模健康和经济破坏。通过对14名COVID-19幸存者的4,277个SARS-CoV-2刺突蛋白特异性记忆B细胞进行单细胞分选,鉴定出453种中和抗体。最有效的中和抗体识别刺突蛋白受体结合结构域,其次是识别S1结构域、刺突蛋白三聚体和S2亚基的抗体。只有1.4%的菌株能中和真实病毒,效价为1-10 ng/mL。最有效的单克隆抗体,经工程改造,以降低抗体依赖性增强的风险和延长半衰期,中和了真正的野生型病毒和含有D 614 G,E484 K和N501 Y取代的新变体。在不存在Fc功能的情况下,分别在0.25和4 mg/kg剂量下观察到仓鼠模型的预防和治疗疗效。极有效的中和人单克隆抗体虽然罕见,但从COVID-19康复期患者中分离出来,适用于野生型SARS-CoV-2以及新出现的变体的预防和治疗干预。
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. Extremely potent neutralizing human monoclonal antibodies, though rare, are isolated from COVID-19 convalescent patients and suitable for prophylactic and therapeutic interventions of wild-type SARS-CoV-2 as well as emerging variants.
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