美国Vir生物技术公司Gyorgy Snell等研究人员合作发现，目前传播中的SARS-CoV-2突刺N439K变异体能够逃逸抗体免疫，并且不影响其致病性。相关论文于2021年1月28日在线发表于国际学术期刊《细胞》。
研究人员证明了免疫显性的SARS-CoV-2突刺（S）受体结合基序（RBM）是S的高度可变区域，并提供了当前RBM突变N439K的流行病学、临床和分子表征。研究人员证明N439K S蛋白具有增强的hACE2受体结合亲和力，并且N439K病毒具有相似的体外复制适应性，与野生型相比具有相似的临床结局。
研究人员发现，N439K突变赋予了对几种中和性单克隆抗体（包括由FDA授权紧急使用的一种抗性）的抗性，并降低了恢复人群的一些多克隆血清的活性。在SARS-CoV-2 S内可能会出现诸如N439K之类的免疫逃逸突变，这突出表明了科学家需要进行持续的分子监测来指导疫苗和治疗剂的开发和使用。
据了解，SARS-CoV-2可以突变并逃避免疫，从而影响疫苗和抗体治疗剂的功效。
附：英文原文
Title: Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
Author: Emma C. Thomson, Laura E. Rosen, James G. Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A. Wojcechowskyj, Chris Davis, Luca Piccoli, David J. Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O’Toole, Dora Pinto, Rachel M. Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B. Sreenu, Jay Nix, Ivy Zhang, Ruth F. Jarrett, William G. Glass, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Tristan I. Croll, Natasha Johnson, Julia Di Iulio, Arthur Wickenhagen, Alessandro Ceschi, Aoife M. Harbison, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Marco Schiuma, Malcolm G. Semple, Peter J.M. Openshaw, Elisa Fadda, J. Kenneth Baillie, John D. Chodera, Suzannah J. Rihn, Samantha J. Lycett, Herbert W. Virgin, Amalio Telenti, Davide Corti, David L. Robertson, Gyorgy Snell
Issue&Volume: 2021-01-28
Abstract: SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild-type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the FDA, and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.
DOI: 10.1016/j.cell.2021.01.037
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00080-5