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Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination
Immunity ( IF 25.5 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.immuni.2021.08.001
Mark M Painter 1 , Divij Mathew 1 , Rishi R Goel 1 , Sokratis A Apostolidis 2 , Ajinkya Pattekar 3 , Oliva Kuthuru 4 , Amy E Baxter 4 , Ramin S Herati 5 , Derek A Oldridge 6 , Sigrid Gouma 7 , Philip Hicks 7 , Sarah Dysinger 7 , Kendall A Lundgreen 7 , Leticia Kuri-Cervantes 8 , Sharon Adamski 3 , Amanda Hicks 3 , Scott Korte 3 , Josephine R Giles 9 , Madison E Weirick 7 , Christopher M McAllister 7 , Jeanette Dougherty 4 , Sherea Long 4 , Kurt D'Andrea 4 , Jacob T Hamilton 10 , Michael R Betts 8 , Paul Bates 7 , Scott E Hensley 7 , Alba Grifoni 11 , Daniela Weiskopf 11 , Alessandro Sette 11 , Allison R Greenplate 1 , E John Wherry 12
Affiliation  

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.



中文翻译:


抗原特异性 CD4+ T 细胞的快速诱导与针对 SARS-CoV-2 mRNA 疫苗接种的协调体液和细胞免疫相关



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。

更新日期:2021-09-14
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