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A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-26 , DOI: 10.4049/jimmunol.2000583
Wafaa B Alsoussi 1 , Jackson S Turner 1 , James B Case 2 , Haiyan Zhao 1 , Aaron J Schmitz 1 , Julian Q Zhou 3 , Rita E Chen 2 , Tingting Lei 1 , Amena A Rizk 1 , Katherine M McIntire 1 , Emma S Winkler 1, 2 , Julie M Fox 2 , Natasha M Kafai 1, 2 , Larissa B Thackray 2 , Ahmed O Hassan 2 , Fatima Amanat 4, 5 , Florian Krammer 4 , Corey T Watson 6 , Steven H Kleinstein 3, 7, 8 , Daved H Fremont 1, 9, 10 , Michael S Diamond 1, 2, 9, 11 , Ali H Ellebedy 9, 11, 12
Affiliation  

Key Points Generation and screening of anti–SARS-CoV-2 RBD mAbs reveal a potently protective Ab. mAb 2B04 potently neutralizes SARS-CoV-2 in vitro. mAb 2B04 protects mice from morbidity in a murine model of SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

中文翻译:

一种强效中和抗体可保护小鼠免受 SARS-CoV-2 感染

抗 SARS-CoV-2 RBD mAb 的生成和筛选揭示了一种有效的保护性抗体。mAb 2B04 在体外可有效中和 SARS-CoV-2。mAb 2B04 可保护 SARS-CoV-2 感染小鼠模型中的小鼠免受发病。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 导致全球数百万人感染和数十万人死亡。目前还没有针对 SARS-CoV-2 的广泛可用的获得许可的疗法,这突出表明迫切需要有效的干预措施。该病毒通过其三聚体刺突糖蛋白内的受体结合结构域与人血管紧张素转换酶 2 结合进入宿主细胞。在本文中,我们描述了一组针对受体结合结构域的鼠 mAb 的生成和表征。一种单克隆抗体 2B04 在体外中和野生型 SARS-CoV-2,具有显着的效力(半数最大抑制浓度 <2 ng/ml)。在 SARS-CoV-2 感染的小鼠模型中,2B04 可以保护受感染的动物免于体重减轻、降低肺部病毒载量并阻止全身传播。因此,2B04 是一种有希望的候选有效抗病毒药物,可用于预防 SARS-CoV-2 感染。
更新日期:2020-06-26
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