Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
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DOI：
10.1126/science.abd0831
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发表时间：
2020-08-21
期刊：
影响因子：
56.9
通讯作者：
Kyratsous, Christos A.
中科院分区：
文献类型：
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作者：
Baum, Alina;Fulton, Benjamin O.;Kyratsous, Christos A.
针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突蛋白的抗体为对抗 2019 年冠状病毒病 (COVID-19) 大流行提供了一种有前景的方法；然而，人们仍然担心突变会产生抗体抗性。我们研究了针对刺突蛋白的四种抗体的耐药性的发展，这些抗体可以单独或组合成混合物来有效中和 SARS-CoV-2。这些抗体对于人类中出现的尖峰变异仍然有效。然而，在存在单个抗体的情况下体外传代后，新的刺突突变体迅速出现，导致中和作用丧失：结合不同但重叠的刺突蛋白区域的抗体组合也会发生这种逃逸。用非竞争性抗体混合物处理后，没有产生逃逸突变体。
Antibodies targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present a promising approach to combat the coronavirus disease 2019 (COVID-19) pandemic; however, concerns remain that mutations can yield antibody resistance. We investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared after in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization: such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Escape mutants were not generated after treatment with a noncompeting antibody cocktail.