Jones Bryan E, Brown-Augsburger Patricia L, Corbett Kizzmekia S, Westendorf Kathryn, Davies Julian, Cujec Thomas P, Wiethoff Christopher M, Blackbourne Jamie L, Heinz Beverly A, Foster Denisa, Higgs Richard E, Balasubramaniam Deepa, Wang Lingshu, Bidshahri Roza, Kraft Lucas, Hwang Yuri, Žentelis Stefanie, Jepson Kevin R, Goya Rodrigo, Smith Maia A, Collins David W, Hinshaw Samuel J, Tycho Sean A, Pellacani Davide, Xiang Ping, Muthuraman Krithika, Sobhanifar Solmaz, Piper Marissa H, Triana Franz J, Hendle Jorg, Pustilnik Anna, Adams Andrew C, Berens Shawn J, Baric Ralph S, Martinez David R, Cross Robert W, Geisbert Thomas W, Borisevich Viktoriya, Abiona Olubukola, Belli Hayley M, de Vries Maren, Mohamed Adil, Dittmann Meike, Samanovic Marie, Mulligan Mark J, Goldsmith Jory A, Hsieh Ching-Lin, Johnson Nicole V, Wrapp Daniel, McLellan Jason S, Barnhart Bryan C, Graham Barney S, Mascola John R, Hansen Carl L, Falconer Ester
bioRxiv. 2020 Oct 9:2020.09.30.318972. doi: 10.1101/2020.09.30.318972.
SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection.
LY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)构成了公共卫生威胁,迫切需要治疗药物。在此,我们报告,通过对抗原特异性B细胞进行高通量微流控筛选,从一名康复的COVID-19患者中鉴定出一种有效的抗刺突中和抗体LY-CoV555。生化、结构和功能表征显示其与受体结合域具有高亲和力结合、抑制血管紧张素转换酶2(ACE2)结合以及强大的中和活性。在恒河猴攻毒模型中,低至2.5毫克/千克的预防剂量可减少上、下呼吸道中的病毒复制。这些数据表明,高通量筛选可鉴定出一种有效的抗病毒抗体,其能预防SARS-CoV-2感染。
LY-CoV555是一种源自康复COVID-19患者的抗刺突抗体,能有效中和SARS-CoV-2,并保护非人类灵长类动物的上、下呼吸道免受SARS-CoV-2感染。