Prolonged intervals during Mycobacterium tuberculosis subunit vaccine boosting contributes to eliciting immunity mediated by central memory-like T cells
Prolonged intervals during Mycobacterium tuberculosis subunit vaccine boosting contributes to eliciting immunity mediated by central memory-like T cells
复制标题
结核分枝杆菌亚单位疫苗加强接种期间的延长间隔有助于激发由中枢记忆样 T 细胞介导的免疫
DOI：
10.1016/j.tube.2018.04.006
复制
发表时间：
2018-05-01
期刊：
影响因子：
3.2
通讯作者：
Zhu, Bingdong
中科院分区：
文献类型：
--
作者：
Bai, Chunxiang;He, Juanjuan;Zhu, Bingdong
据信，中央记忆T细胞（T-CM）提供针对结核病（TB）的长期保护。然而，结核病亚单位疫苗免疫程序，特别是免疫间隔时间对T细胞免疫记忆的影响尚不清楚。在本研究中，根据以下时间表，用基于融合蛋白ESAT 6-Ag 85 B-MPT 64（190-198）-Mtb8.4-Rv 2626 c（LT 70）的亚单位疫苗免疫小鼠三次：（1）0、3、6周（0-3- 6周）;（2）0、4、12周（0-4- 12周）;（3）0、4、24周（0- 424周）。结果发现，0-4- 12周和0-4- 24周两种免疫程序均诱导了较高水平的抗原特异性IL-2、IFN-γ和TNF-α，而0-3- 6周免疫则诱导了较高水平的抗原特异性IL-2、IFN-γ和TNF-α。其中，0-4- 12周诱导的IL-2水平最高，IL-2是主要由T-CM产生的关键细胞因子。此外，通过培养的IFN-γ ELISPOT和细胞增殖测定等，我们发现，0-4- 12周的疫苗接种程序引起更多的T-CM样细胞，更强的T-CM介导的免疫应答和更高的抗M的保护效力。0-3- 6周Bovis BCG攻毒组与0-3- 6周Bovis BCG攻毒组相比，提示在一定程度上延长结核亚单位疫苗的免疫间隔有助于诱导更多的T-CM样细胞，从而提供更强的抗分枝杆菌感染的免疫保护。
It is believed that central memory T cells (T-CM) provide long-term protection against tuberculosis (TB). However, the effects of TB subunit vaccine immunization schedule, especially the vaccination intervals, on T cell immune memory is still unclear. In this study, mice were immunized with fusion protein ESAT6-Ag85B-MPT64 (190-198)-Mtb8.4-Rv2626c (LT70) based subunit vaccine three times according to the following schedules: (1) 0, 3rd and 6th week respectively (0-3-6w), (2) 0, 4th and 12th week (0-4-12w), and (3) 0, 4th and 24th week (0-424w). We found that both schedules of 0-4-12w and 0-4-24w induced higher level of antigen specific IL-2, IFN-gamma and TNF-alpha than 0-3-6w immunization. Among them, 0-4-12w induced the highest level of IL-2, which is a key cytokine mainly produced by T-CM. Moreover, by cultured IFN-gamma ELISPOT and cell proliferation assay etc., we found that the vaccination schedule of 0-4-12w elicited higher numbers of T-CM like cells, stronger T-CM mediated immune responses and higher protective efficacy against M. bovis BCG challenge than 0-3-6w did. It suggests that prolonging the vaccination interval of TB subunit vaccine to some extent contributes to inducing more abundant T-CM like cells and providing stronger immune protection against mycobacteria infection.