Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

中文翻译：

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尖峰突变对SARS-CoV-2中和的影响

多种SARS-CoV-2疫苗已显示出保护功效，这很可能是由中和识别病毒进入蛋白Spike的抗体介导的。来自SARS-CoV-2感染的抗体可通过针对性靶向Spike来中和病毒，并且密切相关的SARS-CoV的血清交叉中和作用有限。由于新的SARS-CoV-2变种正在迅速出现，例如B.1.1.7、501Y.V2和P.1血统，因此了解是否由原始SARS-CoV-2病毒感染引起的抗体反应至关重要或目前的疫苗将仍然有效对抗病毒变种。在这项研究中，我们评估了一系列突变的Spike假型的中和性，包括B.1.1.7 Spike假型。对一组Spike特异性单克隆抗体的分析表明，Spike突变会显着降低某些抗体的中和活性。相比之下，2020年初感染的患者血清中的多克隆抗体仍对大多数突变的Spike假型具有活性。大多数血清样品同样具有中和B.1.1.7 Spike假型的能力，但是少数样品（36个样品中的3个）的效价降低了5-10倍。这项工作突显了SARS-CoV-2 Spike的变化可以改变中和敏感性，并强调了需要有效实时监测新兴突变及其对疫苗功效的影响。2020年初感染的患者血清中的多克隆抗体仍对大多数突变的Spike假型具有活性。大多数血清样品同样具有中和B.1.1.7 Spike假型的能力，但是少数样品（36个样品中的3个）的效价降低了5-10倍。这项工作突显了SARS-CoV-2 Spike的变化可以改变中和敏感性，并强调了需要有效实时监测新兴突变及其对疫苗功效的影响。2020年初感染的患者血清中的多克隆抗体仍对大多数突变的Spike假型具有活性。大多数血清样品同样具有中和B.1.1.7 Spike假型的能力，但是少数样品（36个样品中的3个）的效价降低了5-10倍。这项工作突显了SARS-CoV-2 Spike的变化可以改变中和敏感性，并强调了需要有效实时监测新兴突变及其对疫苗功效的影响。