小柯机器人

研究揭示SARS-CoV-2抗体免疫的演化进程
2021-01-21 10:45

美国洛克菲勒大学Michel C. Nussenzweig等研究人员合作揭示出SARS-CoV-2抗体免疫的演化进程。2021年1月18日,《自然》杂志在线发表了这项成果。

据研究人员介绍,SARS-CoV-2已感染了7800万人,迄今为止造成超过170万人死亡。感染与不同水平中和活性抗体的形成有关,这些抗体可以保护动物模型免受感染。抗体水平随时间降低,但是目前尚未测试记忆B细胞(在重新感染后能够产生抗体)的性质和质量。

研究人员报道了感染1.3个月和6.2个月后评估的87个队列中的体液记忆反应。研究人员发现,IgA和IgG抗SARS-CoV-2突刺蛋白受体结合域(RBD)抗体滴度显著降低,而IgA受的影响较小。同时,在假型病毒分析中血浆中和活性降低了五倍。相反,RBD特定的记忆B细胞的数量不变。记忆B细胞在6.2个月后显示出克隆更新,它们表达的抗体具有更大的体细胞超突变、增强的效力和对RBD突变的抵抗力,这表明了体液反应的持续发展。

通过免疫荧光或聚合酶链反应分析COVID-19发作4个月后从无症状个体获得的肠活检样本,结果揭示了14名志愿者中有7名小肠中SARS-CoV-2核酸的持久性和免疫反应性。研究人员认为,感染后1.3到6.2个月之间,对SARS-CoV-2的记忆B细胞反应以与抗原持久性一致的方式发生演化。

附:英文原文

Title: Evolution of antibody immunity to SARS-CoV-2

Author: Christian Gaebler, Zijun Wang, Julio C. C. Lorenzi, Frauke Muecksch, Shlomo Finkin, Minami Tokuyama, Alice Cho, Mila Jankovic, Dennis Schaefer-Babajew, Thiago Y. Oliveira, Melissa Cipolla, Charlotte Viant, Christopher O. Barnes, Yaron Bram, Galle Breton, Thomas Hgglf, Pilar Mendoza, Arlene Hurley, Martina Turroja, Kristie Gordon, Katrina G. Millard, Victor Ramos, Fabian Schmidt, Yiska Weisblum, Divya Jha, Michael Tankelevich, Gustavo Martinez-Delgado, Jim Yee, Roshni Patel, Juan Dizon, Cecille Unson-OBrien, Irina Shimeliovich, Davide F. Robbiani, Zhen Zhao, Anna Gazumyan, Robert E. Schwartz, Theodora Hatziioannou, Pamela J. Bjorkman, Saurabh Mehandru, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig

Issue&Volume: 2021-01-18

Abstract: 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 models1,2. 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 titres decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold 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 the onset of coronavirus disease-2019 (COVID-19), 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.

DOI: 10.1038/s41586-021-03207-w

Source: https://www.nature.com/articles/s41586-021-03207-w

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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