Co-administration of α-GalCer analog and TLR4 agonist induces robust CD8(+) T-cell responses to PyCS protein and WT-1 antigen and activates memory-like effector NKT cells.
Co-administration of α-GalCer analog and TLR4 agonist induces robust CD8(+) T-cell responses to PyCS protein and WT-1 antigen and activates memory-like effector NKT cells.
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DOI：
10.1016/j.clim.2016.04.014
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Tsuji M
中科院分区：
文献类型：
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作者：
Coelho-Dos-Reis JG;Huang J;Tsao T;Pereira FV;Funakoshi R;Nakajima H;Sugiyama H;Tsuji M
在本研究中，评价了7 DW 8 -5（一种有效的α-GalCer类似物）和单磷酰脂质A（MPLA）（一种TLR 4激动剂）对疫苗诱导的CD 8 + T细胞应答和保护性免疫诱导的联合佐剂效应。用对应于疟疾抗原的CD 8 + T细胞表位的肽、约氏疟原虫的环子孢子蛋白和肿瘤抗原、Wilms肿瘤抗原-1（WT-1）以及作为佐剂的7 DW 8 -5和MPLA免疫小鼠。这些免疫方案能够诱导更高水平的CD 8 + T细胞应答，并且最终，与用与单独的7 DW 8 -5或MPLA混合的肽免疫诱导的水平相比，增强了针对疟疾和肿瘤攻击的保护水平。7 DW 8 -5和MPLA的共同给药诱导记忆样效应自然杀伤T（NKT）细胞（即CD 44 + CD 62 L-NKT细胞）的活化。我们的研究表明，当与MPLA共同施用时，7 DW 8 -5极大地增强了与记忆免疫应答相关的重要协同途径，从而使这种佐剂组合成为新型疫苗佐剂制剂。
In the present study, the combined adjuvant effect of 7DW8-5, a potent α-GalCer-analog, and monophosphoryl lipid A (MPLA), a TLR4 agonist, on the induction of vaccine-induced CD8+ T-cell responses and protective immunity was evaluated. Mice were immunized with peptides corresponding to the CD8+ T-cell epitopes of a malaria antigen, a circumsporozoite protein of Plasmodium yoelii, and a tumor antigen, a Wilms Tumor antigen-1 (WT-1), together with 7DW8-5 and MPLA, as an adjuvant. These immunization regimens were able to induce higher levels of CD8+ T-cell responses and, ultimately, enhanced levels of protection against malaria and tumor challenges compared to the levels induced by immunization with peptides mixed with 7DW8-5 or MPLA alone. Co-administration of 7DW8-5 and MPLA induces activation of memory-like effector natural killer T (NKT) cells, i.e. CD44+CD62L−NKT cells. Our study indicates that 7DW8-5 greatly enhances important synergistic pathways associated to memory immune responses when co-administered with MPLA, thus rendering this combination of adjuvants a novel vaccine adjuvant formulation.