Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
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DOI：
10.1016/j.cell.2021.01.037
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发表时间：
2021-03-04
期刊：
影响因子：
64.5
通讯作者：
Snell G
中科院分区：
文献类型：
--
作者：
Thomson EC;Rosen LE;Shepherd JG;Spreafico R;da Silva Filipe A;Wojcechowskyj JA;Davis C;Piccoli L;Pascall DJ;Dillen J;Lytras S;Czudnochowski N;Shah R;Meury M;Jesudason N;De Marco A;Li K;Bassi J;O'Toole A;Pinto D;Colquhoun RM;Culap K;Jackson B;Zatta F;Rambaut A;Jaconi S;Sreenu VB;Nix J;Zhang I;Jarrett RF;Glass WG;Beltramello M;Nomikou K;Pizzuto M;Tong L;Cameroni E;Croll TI;Johnson N;Di Iulio J;Wickenhagen A;Ceschi A;Harbison AM;Mair D;Ferrari P;Smollett K;Sallusto F;Carmichael S;Garzoni C;Nichols J;Galli M;Hughes J;Riva A;Ho A;Schiuma M;Semple MG;Openshaw PJM;Fadda E;Baillie JK;Chodera JD;ISARIC4C Investigators;COVID-19 Genomics UK (COG-UK) Consortium;Rihn SJ;Lycett SJ;Virgin HW;Telenti A;Corti D;Robertson DL;Snell G
SARS-CoV-2 可以突变并逃避免疫，从而影响新兴疫苗和抗体疗法的功效。在这里，我们证明免疫显性的 SARS-CoV-2 刺突 (S) 受体结合基序 (RBM) 是 S 的高度可变区域，并提供了流行的前哨 RBM 突变 N439K 的流行病学、临床和分子特征。我们证明 N439K S 蛋白与 hACE2 受体的结合亲和力增强，并且与野生型病毒相比，N439K 病毒具有相似的体外复制适应性，并引起具有相似临床结果的感染。我们发现，N439K 突变赋予了对几种中和单克隆抗体的抗性，其中包括美国食品和药物管理局 (FDA) 授权紧急使用的一种单克隆抗体，并降低了感染康复者的一些多克隆血清的活性。 SARS-CoV-2 S 中可能会出现保持毒力和适应性的免疫逃避突变（例如 N439K），这凸显了持续进行分子监测以指导疫苗和治疗方法的开发和使用的必要性。受体结合基序 (RBM) 是 SARS-CoV-2 刺突的高度可变区域 RBM 突变 N439K 在多个谱系中独立出现 N439K 增加了对 hACE2 的刺突亲和力；病毒适应性和疾病不变 N439K 赋予对几种 mAb 的抗性并逃避一些多克隆反应 SARS-CoV-2 刺突受体结合基序中 N439K 突变的流行病学、临床、分子和结构特征表明，与野生型相比，它会导致类似的病毒适应性，同时赋予对一些中和单克隆抗体的抗性并降低一些多克隆抗体反应的活性。
SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, 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 US Food and Drug Administration (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. The receptor-binding motif (RBM) is a highly variable region of SARS-CoV-2 spike RBM mutation N439K has emerged independently in multiple lineages N439K increases spike affinity for hACE2; viral fitness and disease are unchanged N439K confers resistance to several mAbs and escapes some polyclonal responses Epidemiological, clinical, molecular, and structural characterization of the N439K mutation in the SARS-CoV-2 spike receptor binding motif demonstrates that it results in similar viral fitness compared to wild-type while conferring resistance against some neutralizing monoclonal antibodies and reducing the activity of some polyclonal antibody responses.
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影响因子：
7.7
作者：
Weisblum Y;Schmidt F;Zhang F;DaSilva J;Poston D;Lorenzi JC;Muecksch F;Rutkowska M;Hoffmann HH;Michailidis E;Gaebler C;Agudelo M;Cho A;Wang Z;Gazumyan A;Cipolla M;Luchsinger L;Hillyer CD;Caskey M;Robbiani DF;Rice CM;Nussenzweig MC;Hatziioannou T;Bieniasz PD
通讯作者：
Bieniasz PD
DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
超越屏蔽：聚糖在SARS-COV-2尖峰蛋白中的作用。
影响因子：
18.2
作者：
Casalino L;Gaieb Z;Goldsmith JA;Hjorth CK;Dommer AC;Harbison AM;Fogarty CA;Barros EP;Taylor BC;McLellan JS;Fadda E;Amaro RE
通讯作者：
Amaro RE
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS