An antibody cocktail against SARS-CoV-2 There is an urgent focus on antibodies that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral spike and prevent the virus from entering host cells. Hansen et al. generated a large panel of antibodies against the spike protein from humanized mice and recovered patients. From this panel, they identified several neutralizing antibodies, including pairs that do not compete for binding to the receptor binding domain. Baum et al. focused in on four of these antibodies. All four are effective against known spike variants. However, by growing a pseudovirus that expresses the spike in the presence of individual antibodies, the authors were able to select for spike mutants resistant to that antibody. In contrast, escape mutants are not selected when pseudovirus is grown in the presence of pairs of antibodies that either do not compete or only partially compete for binding to the RBD. Such a pair might be used in a therapeutic antibody cocktail. Science, this issue p. 1010, p. 1014 A noncompeting antibody cocktail to SARS-CoV-2 spike protein safeguards against the ability of virus mutations to lead to antibody resistance. 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.

中文翻译：

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针对 SARS-CoV-2 刺突蛋白的抗体混合物可防止单个抗体的快速突变逃逸

针对 SARS-CoV-2 的抗体混合物 人们迫切关注针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病毒刺突并阻止病毒进入宿主细胞的抗体。汉森等人。从人源化小鼠和康复患者身上产生了大量针对刺突蛋白的抗体。从该组中，他们鉴定了几种中和抗体，包括不竞争与受体结合结构域结合的抗体对。鲍姆等人。重点关注其中四种抗体。这四种病毒均能有效对抗已知的尖峰变体。然而，通过培养在存在单个抗体的情况下表达刺突的假病毒，作者能够选择对该抗体具有抗性的刺突突变体。相反，当假病毒在不竞争或仅部分竞争结合RBD的抗体对存在的情况下生长时，不会选择逃逸突变体。这样的一对可用于治疗性抗体混合物中。科学，本期第 14 页。1010，p。1014 针对 SARS-CoV-2 刺突蛋白的非竞争性抗体混合物可防止病毒突变导致抗体耐药性。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，在个体抗体存在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；这种逃逸也发生在结合不同但重叠的刺突蛋白区域的抗体组合中。用非竞争性抗体混合物处理后，没有产生逃逸突变体。