SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4⁺ T cell responses in naive subjects after the first dose, whereas CD8⁺ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8⁺ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4⁺ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.

SARS-CoV-2 mRNA 疫苗已显示出显着的临床疗效，但 T 细胞启动的性质和动力学仍存在疑问。我们在 mRNA 初次接种和加强疫苗接种之前和之后对健康的 SARS-CoV-2 首次接触者和康复个体进行了纵向抗原特异性 T 细胞分析。第一次接种后，疫苗接种在首次接种的受试者中诱导了快速的抗原特异性 CD4 ⁺ T 细胞反应，而 CD8 ⁺ T 细胞反应逐渐发展，且程度各异。第一次接种后疫苗诱导的 Th1 和 Tfh 细胞反应分别与加强后 CD8 ⁺ T 细胞和中和抗体相关。综合分析显示，在 SARS-CoV-2 首次接触者和康复者中，协调的免疫反应具有不同的轨迹。最后，虽然加强疫苗接种可以改善 SARS-CoV-2 初治受试者的 T 细胞反应，但第二剂疫苗对 SARS-CoV-2 康复者几乎没有效果。这些发现强调了快速启动的 CD4 ⁺ T 细胞在协调 SARS-CoV-2 初治个体对第二剂疫苗的反应中的作用。