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. Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola—one from genetically humanized mice and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that were characterized for binding, neutralization, and three-dimensional structure. On the basis of these criteria, we selected pairs of highly potent individual antibodies that simultaneously bind the receptor binding domain of the spike protein, thereby providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single-antibody treatment.

中文翻译：

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对人源化小鼠和恢复期人类的研究产生了一种 SARS-CoV-2 抗体鸡尾酒

一种针对 SARS-CoV-2 的抗体鸡尾酒 针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 病毒尖峰并防止病毒进入宿主细胞的抗体受到紧急关注。汉森等人。从人源化小鼠和康复患者中产生了大量针对刺突蛋白的抗体。从该小组中，他们确定了几种中和抗体，包括不竞争结合受体结合域的抗体对。鲍姆等人。专注于其中四种抗体。所有四种都对已知的尖峰变体有效。然而，通过培养在单个抗体存在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。相比之下，当假病毒在不竞争或仅部分竞争与 RBD 结合的抗体对的存在下生长时，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。科学，这个问题 p。1010 页。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抗性。中和抗体已成为治疗传染病的重要工具。最近，两种不同的方法产生了成功的埃博拉抗体治疗——一种来自基因人源化小鼠，另一种来自人类幸存者。在这里，我们描述了使用人源化小鼠和恢复期患者产生针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突蛋白的抗体的平行工作，这产生了大量全人源抗体，其特征在于结合、中和和三维结构。在这些标准的基础上，我们选择了一对同时结合刺突蛋白的受体结合域的高效个体抗体，从而为治疗性抗体鸡尾酒提供了理想的合作伙伴，旨在降低可能出现的病毒逃逸突变体的可能性。对来自单抗体治疗的选择压力的反应。