A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters.

A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters.
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DOI:
10.3389/fimmu.2020.614256
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发表时间:
2020
影响因子:
7.3
通讯作者:
Schountz T
Schountz T
中科院分区:
医学2区
文献类型:
--
作者:
Fagre AC;Manhard J;Adams R;Eckley M;Zhan S;Lewis J;Rocha SM;Woods C;Kuo K;Liao W;Li L;Corper A;Challa D;Mount E;Tumanut C;Tjalkens RB;Aboellail T;Fan X;Schountz T

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COVID-19的出现导致了一场大流行病,导致数百万例疾病、不同的发病率和数十万人死亡。目前,只有瑞德西韦和地塞米松显示出有限的疗效,仅略微减轻疾病负担,因此需要新的方法用于COVID-19的临床管理。我们从酵母展示文库中鉴定了一组对SARS-CoV-2刺突蛋白受体结合结构域具有特异性的人单克隆抗体克隆,所述刺突蛋白受体结合结构域在体外中和病毒。给用SARS-CoV-2攻击的叙利亚仓鼠施用先导抗体克隆显著降低了肺中的病毒载量和组织病理学评分。此外,抗体中断单核细胞浸润到肺中,这可能有助于通过限制免疫病理学恶化来降低疾病严重程度。使用这种抗体可以为COVID-19患者的治疗提供重要的疗法。
The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.