小柯机器人

2021年3月16日，《细胞》杂志在线发表了美国哈佛医学院Jonathan Abraham小组的最新成果，他们发现免疫功能低下宿主中的SARS-CoV-2进化可揭示出共有的中和逃逸机制。

为了深入了解病毒刺突（S）蛋白受体结合域（RBD）如何响应常见的抗体反应而进化，研究人员测试了在病毒进化期间持续感染的免疫功能低下个体中发生的突变。研究人员使用了抗体Fab/RBD结构来预测，并使用假型病毒来确认在晚期进化的S变体中发现的突变，能够对COVID-19恢复期患者中分离出的一类常见SARS-CoV-2中和抗体具有抗性。抗药性延伸至被测试的四个恢复期患者中的四个多克隆血清免疫球蛋白，以及临床使用中的单克隆抗体。

研究人员进一步表明，亲和力成熟对于野生型病毒中和并不重要，但对中和广度至关重要。由于这些研究的突变预示了正在全球范围内传播的新兴变体，因此这些结果对S相关对策的长期有效性产生了影响。

据悉，许多个体对SARS-CoV-2的抗体反应几乎相同。

附：英文原文

Title: SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms

Author: Sarah A. Clark, Lars E. Clark, Junhua Pan, Adrian Coscia, Lindsay G.A. McKay, Sundaresh Shankar, Rebecca I. Johnson, Vesna Brusic, Manish C. Choudhary, James Regan, Jonathan Z. Li, Anthony Griffiths, Jonathan Abraham

Issue&Volume: 2021-03-16

Abstract: Many individuals mount nearly identical antibody responses to SARS-CoV-2. To gain insight into how the viral spike (S) protein receptor-binding domain (RBD) might evolve in response to common antibody responses, we studied mutations occurring during virus evolution in a persistently infected immunocompromised individual. We use antibody Fab/RBD structures to predict, and pseudotypes to confirm, that mutations found in late-stage evolved S variants confer resistance to a common class of SARS-CoV-2 neutralizing antibodies we isolated from a healthy COVID-19 convalescent donor. Resistance extends to the polyclonal serum immunoglobulins of four out of four healthy convalescent donors we tested and to monoclonal antibodies in clinical use. We further show that affinity maturation is unimportant for wildtype virus neutralization but is critical to neutralization breadth. As the mutations we studied foreshadowed emerging variants that are now circulating across the globe, our results have implications to the long-term efficacy of S-directed countermeasures.

DOI: 10.1016/j.cell.2021.03.027

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00355-X