Evolution of antibody immunity to SARS-CoV-2.
Evolution of antibody immunity to SARS-CoV-2.
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DOI：
10.1038/s41586-021-03207-w
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
--
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
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已感染7800万人，迄今造成170多万人死亡。在动物模型中，感染与具有中和活性的不同水平的抗体的产生有关，这种抗体可以预防感染。抗体水平随着时间的推移而下降，但据我们所知，在再次感染时产生抗体所需的记忆B细胞的性质和质量尚未得到检查。在这里，我们报告了87名个体在感染SARS-CoV-2后1.3个月和6.2个月的体液记忆反应。我们发现，抗SARS-CoV-2刺突蛋白受体结合域(RBD)的IgM和IgG抗体滴度在这段时间内显著下降，其中IgA受到的影响较小。同时，在伪型病毒检测中，血浆中和活性降低了五倍。相比之下，RBD特异性记忆B细胞的数量在感染后6.2个月保持不变。记忆B细胞在6.2个月后表现出克隆性更新，它们表达的抗体具有更大的体细胞超突变、对RBD突变的抵抗力和增强的效力，表明体液反应继续进化。对无症状个体在2019年冠状病毒病(新冠肺炎)发病后4个月的肠道活检进行的免疫荧光和聚合酶链式反应分析显示，14人中有7人的小肠中存在SARS-CoV-2核酸和免疫反应。我们得出结论，记忆B细胞对SARS-CoV-2的反应在感染后1.3到6.2个月之间以一种与抗原持久性一致的方式进化。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
3.4
作者：
GUY, HR
通讯作者：
GUY, HR
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N