mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection [CV4]. mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection [CV4]

SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell dataset of peripheral blood of patients with acute COVID-19 and of healthy volunteers before and after receiving the SARS-CoV-2 mRNA vaccine and booster. We compared host immune responses to the virus and vaccine using transcriptional profiling, coupled with B/T cell receptor repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. These findings were validated in an independent dataset. Analysis of B and T cell repertoires revealed that, while the majority of clonal lymphocytes in COVID-19 patients were effector cells, clonal expansion was more evident among circulating memory cells in vaccine recipients. Furthermore, while clonal αβ T cell responses were observed in both COVID-19 patients and vaccine recipients, dramatic expansion of clonal gdT cells was found only in infected individuals. Our dataset enables comparative analyses of immune responses to infection versus vaccination, including clonal B and T cell responses. Taken together, our comparative analysis shows that vaccination induces a robust adaptive immune response, including a durable clonal B and T cell response, without the severe inflammation associated with infection. Overall design: We profiled crculating immune cells from five adults with acute COVID-19 infection and nine healthy adults, seven of whom received theBNT162b2 vaccine. For three of the vaccine recipients, samples were also collected before and after receiving a booster. Samples were taken at multiple time points, resulting in a total of 42 post-vaccination and 9 post-infection samples

新型冠状病毒（SARS-CoV-2）感染与疫苗接种均可诱发强效免疫应答。本研究构建了一套全面的多模态单细胞数据集，样本来源包括急性新型冠状病毒肺炎患者的外周血，以及健康志愿者在接种新型冠状病毒信使核糖核酸（mRNA）疫苗及加强针前后的外周血样本。本研究通过转录组分析结合B细胞、T细胞受体库重构，对比了宿主针对病毒与疫苗的免疫应答特征。新型冠状病毒肺炎患者表现出干扰素特征上调与细胞毒性基因表达升高，而疫苗接种者未出现此类变化，上述结论在独立数据集内得到了验证。对B细胞与T细胞受体库的分析显示，新型冠状病毒肺炎患者体内的多数克隆性淋巴细胞为效应细胞；而疫苗接种者的克隆扩增现象则更多见于循环记忆细胞群体中。此外，尽管新型冠状病毒肺炎患者与疫苗接种者均检测到克隆性αβ T细胞应答，但仅在感染个体中观察到克隆性γδ T细胞的显著扩增。本数据集可用于对比分析感染与疫苗接种引发的免疫应答，包括克隆性B细胞与T细胞应答。综上，本研究的对比分析表明，疫苗接种可诱导稳健的适应性免疫应答，包括持久的克隆性B细胞与T细胞应答，且不会伴随感染相关的严重炎症反应。实验设计：我们对5名急性新型冠状病毒感染成人的循环免疫细胞进行了转录组分析，同时纳入9名健康成人，其中7名接受了BNT162b2疫苗接种。其中3名疫苗接种者在加强针接种前后均采集了样本。研究共设置多个采样时间点，最终获得42份疫苗接种后样本与9份感染后样本。