A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.

A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.
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DOI:
10.4049/jimmunol.2000583
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发表时间:
2020-08-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Ellebedy AH
Ellebedy AH
中科院分区:
其他
文献类型:
--
作者:
Alsoussi WB;Turner JS;Case JB;Zhao H;Schmitz AJ;Zhou JQ;Chen RE;Lei T;Rizk AA;McIntire KM;Winkler ES;Fox JM;Kafai NM;Thackray LB;Hassan AO;Amanat F;Krammer F;Watson CT;Kleinstein SH;Fremont DH;Diamond MS;Ellebedy AH

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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是全球数百万感染和数十万死亡的原因。目前还没有针对SARS-CoV-2的广泛可用的许可治疗方法,这突出表明迫切需要有效的干预措施。病毒通过其三聚体刺突糖蛋白内的受体结合结构域(RBD)与人血管紧张素转换酶2结合进入宿主细胞。在这里,我们描述了一组鼠单克隆抗体(mAb)的RBD特异性的生成和表征。其中2B 04单抗在体外中和野生型SARS-CoV-2具有显著的效力(半数最大抑制浓度<2 ng/mL)。在一种新的SARS-CoV-2感染鼠模型中,2B 04可保护受攻击的动物免于体重减轻,降低肺病毒载量,并阻断全身传播。因此,2B 04是一个有希望的候选有效的抗病毒药物,可用于预防SARS-CoV-2感染。
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 (RBD) within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. Here, we describe the generation and characterization of a panel of murine monoclonal antibodies (mAbs) specific for the RBD. One mAb, 2B04, neutralized wild type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/mL). In a novel 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.
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