Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
Nature. 2021 Mar;591(7851):639-644. doi: 10.1038/s41586-021-03207-w. Epub 2021 Jan 18.
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.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)已感染 7800 万人,导致截至目前超过 170 万人死亡。感染与具有中和活性的抗体的产生有关,在动物模型中,这些抗体可以预防感染。抗体水平随时间下降,但据我们所知,尚未研究在再次感染时产生抗体所需的记忆 B 细胞的性质和质量。在这里,我们报告了 87 名个体在感染 SARS-CoV-2 后 1.3 和 6.2 个月时的体液记忆反应。我们发现,针对 SARS-CoV-2 刺突蛋白受体结合域(RBD)的 IgM 和 IgG 抗体的滴度在此期间显著下降,而 IgA 的影响较小。同时,在假型病毒测定中,血浆中的中和活性降低了五倍。相比之下,感染后 6.2 个月时,RBD 特异性记忆 B 细胞的数量保持不变。感染后 6.2 个月时,记忆 B 细胞发生克隆性转换,并且它们表达的抗体具有更多的体细胞超突变、对 RBD 突变的抗性和增强的效力,表明体液反应仍在继续进化。对无症状个体在 COVID-19 发病后 4 个月获得的小肠活检进行免疫荧光和 PCR 分析,发现 14 名个体中有 7 名个体的小肠中仍存在 SARS-CoV-2 核酸和免疫反应性。我们得出结论,在感染后 1.3 至 6.2 个月之间,SARS-CoV-2 的记忆 B 细胞反应以与抗原持续存在一致的方式演变。
Nature. 2021-3
bioRxiv. 2021-1-4
Vaccines (Basel). 2025-7-28
Front Bioeng Biotechnol. 2025-7-8
Science. 2020-10-28