Markers of Memory CD8 T Cells Depicting the Effect of the BNT162b2 mRNA COVID-19 Vaccine in Japan.
Markers of Memory CD8 T Cells Depicting the Effect of the BNT162b2 mRNA COVID-19 Vaccine in Japan.
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DOI：
10.3389/fimmu.2022.836923
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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BNT 162 b2是一种针对SARS-CoV-2刺突糖蛋白（S）的核苷修饰mRNA疫苗，可提供约95%的预防COVID-19的有效性。然而，目前尚不清楚如何有效地产生记忆性CD 8 + T细胞，以及哪些遗传和环境因素影响这种疫苗引起的记忆性CD 8 + T细胞的产生和功能。在这里，我们调查了日本人群第二次接种疫苗后3周记忆性CD 8 + T细胞的频率和功能。使用肽-MHC五聚体，我们检测到的记忆CD 8 + T细胞的数量增加，同时增加血清抗-S蛋白抗体在女性与男性相比，但五聚体阳性细胞的频率与抗体滴度不呈正相关。在CD 8+细胞和五聚体+细胞中的记忆前体效应细胞（KLRG 1-CD 127+）和在五聚体+细胞中的效应细胞（CD 38-HLA-DR+）在女性中比男性更丰富。在S蛋白介导的T细胞刺激后，CD 107 a和颗粒酶B表达的强度在女性中比在男性中增加，表明在女性中比在男性中更强的记忆性CD 8 + T细胞应答。我们的研究表明，在日本人群中，与男性相比，BNT 162 b2疫苗在女性中增强了记忆性CD 8 + T细胞增殖和继发性CTL应答。这些发现为mRNA疫苗接种的细胞免疫应答的性别差异提供了重要依据，并表明记忆前体效应细胞可以作为评估和增强BNT 162 b2诱导的细胞免疫的标志物之一。
BNT162b2, a nucleoside-modified mRNA vaccine for SARS-CoV-2 spike glycoprotein (S), provides approximately 95% efficacy for preventing COVID-19. However, it remains unclear how effectively memory CD8+ T cells are generated and which genetic and environmental factors affect the generation and function of memory CD8+ T cells elicited by this vaccine. Here, we investigated the frequency and functions of memory CD8+ T cells 3 weeks after the second vaccination in the Japanese population. Using a peptide-MHC pentamer, we detected an increased number of memory CD8+ T cells together with increased serum anti-S protein antibody in females compared with that in males, but the frequency of pentamer-positive cells was not positively correlated with antibody titers. Memory precursor effector cells (KLRG1-CD127+) among both CD8+ cells and pentamer+ cells and effector cells (CD38-HLA-DR+) among pentamer+ cells were more abundant in females than in males. Upon S protein-mediated stimulation of T cells, the intensity of CD107a and granzyme B expression was increased in females compared with that in males, indicating stronger memory CD8+ T cell responses in females than in males. Our studies showed that the BNT162b2 vaccine elicits increased memory CD8+ T cell proliferation and secondary CTL responses in females compared with those in males in the Japanese population. These findings provide an important basis for the distinct sex difference in cellular immune responses to mRNA vaccination and suggest that memory precursor effector cells can be one of markers to evaluate and boost cellular immunity induced by BNT162b2.