mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection [CV9]

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 aß 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

SARS-CoV-2感染与疫苗接种均可诱发强效免疫应答。本研究发布一套全面的多模态单细胞数据集（multimodal single-cell dataset），涵盖急性COVID-19患者，以及健康志愿者接种SARS-CoV-2 mRNA疫苗（SARS-CoV-2 messenger RNA vaccine）及加强针前后的外周血样本。本研究通过转录谱分析（transcriptional profiling）结合B细胞受体（B cell receptor）与T细胞受体（T cell receptor）谱系重构，对比了宿主针对病毒与疫苗的免疫应答特征。COVID-19患者体内呈现增强的干扰素特征与细胞毒性基因上调现象，而疫苗接种者未出现此类表达谱变化。上述研究发现已在独立数据集上得到验证。对B、T细胞受体谱系的分析显示：尽管COVID-19患者体内多数克隆性淋巴细胞为效应细胞，但疫苗接种者的循环记忆细胞群中克隆扩增更为显著。此外，尽管在COVID-19患者与疫苗接种者体内均观测到克隆性αβ T细胞应答，但仅在感染个体中发现了克隆性γδ T细胞的显著扩增。本数据集可支持感染与疫苗接种引发的免疫应答的对比分析，包括克隆性B、T细胞应答相关研究。综上，本研究的对比分析表明，疫苗接种可诱导强劲的适应性免疫应答（adaptive immune response），包括持久的克隆性B、T细胞应答，且不会伴随感染相关的严重炎症反应。整体实验设计：我们对5名急性COVID-19感染成人患者与9名健康成人的循环免疫细胞进行了转录谱分析，其中7名健康成人接种了BNT162b2疫苗。3名疫苗接种者在接种加强针前后均采集了样本。本研究采集了多个时间点的样本，最终共获得42份疫苗接种后样本与9份感染后样本。