背景:适应性免疫反应被认为在SARS-CoV-2感染中起关键作用。B细胞的作用,CD4+T,和CD8+T细胞在疫苗诱导的免疫应答中是不同的,因此,探索适应性免疫反应的功能和动力学势在必行。我们从未接种疫苗和接种疫苗的个体收集血液样本。为了评估CoronaVac疫苗的保护性免疫机制,我们绘制了在不同时间点初次接种和加强接种CoronaVac疫苗后体液和细胞免疫应答的动力学和持久性.
方法:我们从血液样品中分离PBMC和血浆。通过流式细胞术和ELISA分析RBD-spcificCD4T和CD8T细胞的分化和功能。通过ELISA分析抗体应答。进行ELISPOT分析以检测RBD-spcific记忆B细胞。进行CBA分析以检测细胞因子免疫谱。使用Graphpad棱镜8和Origin2021进行统计分析。
结果:疫苗诱导的CD4+T细胞对RBD的反应比CD8+T细胞反应更显著,特征为主要的Th1和弱的Th17辅助反应。CoronaVac疫苗引发了主要的IgG1抗体反应,并在加强疫苗接种后有效地召回了针对RBD蛋白的特异性抗体。加强疫苗接种后检测到强健的抗原特异性记忆B细胞(p<0.0001),并在初次疫苗接种后6个月(p<0.0001)维持。疫苗诱导的CD4+T细胞与CD8+T细胞相关(r=0.7147,0.3258,p<0.0001,p=0.04),记忆B细胞反应(r=0.7083,p<0.0001),免疫接种后IgG和IgA(r=0.6168,0.5519,p=0.0006,0.003)。此外,疫苗在早期在血浆中诱导了更广泛和复杂的细胞因子模式。
结论:综合来看,这些结果强调了B细胞和T细胞应答在疫苗诱导的长期免疫中的潜在作用.
Adaptive immune response has been thought to play a key role in SARS-CoV-2 infection. The role of B cells, CD4+T, and CD8+T cells are different in vaccine-induced immune response, thus it is imperative to explore the functions and kinetics of adaptive immune response. We collected blood samples from unvaccinated and vaccinated individuals. To assess the mechanisms contributing to protective immunity of CoronaVac vaccines, we mapped the kinetics and durability of humoral and cellular immune responses after primary and boost vaccination with CoronaVac vaccine in different timepoints.
We separate PBMC and plasma from blood samples. The differentiation and function of RBD-spcific CD4+T and CD8+T cells were analyzed by flow cytometry and ELISA. Antibodies response was analyzed by ELISA. ELISPOT analysis was perfomed to detected the RBD-spcific memory B cells. CBA analysis was performed to detected the cytokine immune profiles. Graphpad prism 8 and Origin 2021 were used for statistical analysis.
Vaccine-induced CD4+T cell responses to RBD were more prominent than CD8+T cell responses, and characterized by a predominant Th1 and weak Th17 helper response. CoronaVac vaccine triggered predominant IgG1 antibody response and effectively recalled specific antibodies to RBD protein after booster vaccination. Robust antigen-specific memory B cells were detected (p < 0.0001) following booster vaccination and maintained at 6 months (p < 0.0001) following primary vaccination. Vaccine-induced CD4+T cells correlated with CD8+T cells (r = 0.7147, 0.3258, p < 0.0001, p = 0.04), memory B cell responses (r = 0.7083, p < 0.0001), and IgG and IgA (r = 0.6168, 0.5519, p = 0.0006, 0.003) after vaccination. In addition, vaccine induced a broader and complex cytokine pattern in plasma at early stage.
Taken together, these results highlight the potential role of B cell and T cell responses in vaccine-induced long-term immunity.