Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Immunity. 2021 Sep 14;54(9):2133-2142.e3. doi: 10.1016/j.immuni.2021.08.001. Epub 2021 Aug 13.
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 疫苗已显示出显著的临床疗效,但关于 T 细胞启动的性质和动力学仍存在疑问。我们在接受 mRNA 疫苗初免和加强免疫之前和之后,对健康的 SARS-CoV-2 初次感染和康复个体进行了纵向抗原特异性 T 细胞分析。初次接种后,在无 SARS-CoV-2 感染史的个体中,疫苗迅速诱导了抗原特异性 CD4 T 细胞反应,而 CD8 T 细胞反应则逐渐发展,且在数量上存在差异。初次接种后诱导的 Th1 和 Tfh 细胞反应分别与加强免疫后的 CD8 T 细胞和中和抗体相关。综合分析显示,初次感染和康复个体的免疫反应具有不同的轨迹和协调方式。最后,加强免疫在 SARS-CoV-2 初次感染个体中改善了 T 细胞反应,而在 SARS-CoV-2 康复个体中,第二剂疫苗的效果很小。这些发现强调了快速启动的 CD4 T 细胞在协调 SARS-CoV-2 初次感染个体对第二剂疫苗的反应中的作用。