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

被引:24
作者
Fagre, Anna C. [1 ]
Manhard, John [2 ]
Adams, Rachel [2 ]
Eckley, Miles [1 ]
Zhan, Shijun [1 ]
Lewis, Juliette [1 ]
Rocha, Savannah M. [3 ]
Woods, Catherine [2 ]
Kuo, Karina [2 ]
Liao, Wuxiang [2 ]
Li, Lin [2 ]
Corper, Adam [2 ]
Challa, Dilip [2 ]
Mount, Emily [2 ]
Tumanut, Christine [2 ]
Tjalkens, Ronald B. [3 ]
Aboellail, Tawfik [1 ]
Fan, Xiaomin [2 ]
Schountz, Tony [1 ]
机构
[1] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
[2] AvantGen Inc, San Diego, CA 92121 USA
[3] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
COVID; monoclonal Ab; SARS-CoV-2; therapeutic antibodies; coronavirus; SYNDROME CORONAVIRUS RECEPTOR; OXIDATIVE STRESS; SPIKE PROTEIN; COVID-19; BINDING; MACROPHAGES; ACTIVATION; INFECTION; MONOCYTE;
D O I
10.3389/fimmu.2020.614256
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页数:13
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