针对新型冠状病毒2(SARS-CoV-2)的抗体免疫的演变
Evolution of Antibody Immunity to SARS-CoV-2.
作者信息
Gaebler Christian, Wang Zijun, Lorenzi Julio C C, Muecksch Frauke, Finkin Shlomo, Tokuyama Minami, Cho Alice, Jankovic Mila, Schaefer-Babajew Dennis, Oliveira Thiago Y, Cipolla Melissa, Viant Charlotte, Barnes Christopher O, Hurley Arlene, Turroja Martina, Gordon Kristie, Millard Katrina G, Ramos Victor, Schmidt Fabian, Weisblum Yiska, Jha Divya, Tankelevich Michael, Yee Jim, Shimeliovich Irina, Robbiani Davide F, Zhao Zhen, Gazumyan Anna, Hatziioannou Theodora, Bjorkman Pamela J, Mehandru Saurabh, Bieniasz Paul D, Caskey Marina, Nussenzweig Michel C, Hagglof Thomas, Schwartz Robert E, Bram Yaron, Martinez-Delgado Gustavo, Mendoza Pilar, Breton Gaelle, Dizon Juan, Unson-O'Brien Cecille, Patel Roshni
出版信息
bioRxiv. 2021 Jan 4:2020.11.03.367391. doi: 10.1101/2020.11.03.367391.
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 development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection 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. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 4 months after coronavirus disease-2019 (COVID-19) onset, using immunofluorescence, or polymerase chain reaction, revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 volunteers. 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.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已感染7800万人,迄今为止造成超过170万人死亡。感染会引发具有中和活性的不同水平抗体的产生,这些抗体在动物模型中可预防感染。抗体水平会随时间下降,但再次感染时负责产生抗体的记忆B细胞的性质和质量尚未得到研究。在此,我们报告了一组87名个体在感染后1.3个月和6.2个月时的体液记忆反应。我们发现,IgM和IgG抗SARS-CoV-2刺突蛋白受体结合域(RBD)抗体滴度显著下降,而IgA受影响较小。同时,在假型病毒试验中,血浆中的中和活性下降了五倍。相比之下,RBD特异性记忆B细胞的数量没有变化。记忆B细胞在6.2个月后出现克隆更替,它们所表达的抗体具有更高的体细胞超突变、更强的效力以及对RBD突变的抗性,这表明体液反应在持续进化。对2019冠状病毒病(COVID-19)发病4个月后无症状个体的肠道活检样本进行免疫荧光或聚合酶链反应分析,发现14名志愿者中有7人的小肠中存在SARS-CoV-2核酸和免疫反应性。我们得出结论,感染后1.3个月至6.2个月期间,记忆B细胞对SARS-CoV-2的反应以与抗原持续存在相一致的方式演变。