Enhancement of DNA vaccine potency by antigen linkage to IFN-γ-inducible protein-10
Enhancement of DNA vaccine potency by antigen linkage to IFN-γ-inducible protein-10
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DOI：
10.1002/ijc.25391
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发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Kim, Tae Woo
中科院分区：
文献类型：
--
作者：
Kang, Tae Heung;Kim, Keon Woo;Kim, Tae Woo
DNA疫苗已成为产生抗原特异性T细胞免疫应答的有吸引力的方法。尽管如此，DNA疫苗的效力仍然需要提高癌症免疫治疗。在这项研究中，我们探讨了是否功能连接的Th 1极化趋化因子，IP-10，一个模型肿瘤抗原，人乳头瘤病毒16型（HPV-16）E7，增强DNA疫苗的效力。IP-10连接改变了E7从细胞核到内质网的位置，并导致功能性化学吸引嵌合IP-10/E7蛋白的分泌。此外，这种连接显著增强了E7抗原通过MHC I类的内源性加工。更重要的是，我们发现皮内接种IP-10/E7 DNA的C57 BL/6小鼠表现出E7特异性CD 4（+）Th 1 T细胞和CD 8（+）T细胞数量的显著增加，因此，与接种野生型E7 DNA的小鼠相比，对表达E7的肿瘤具有长期的强烈抗性。因此，由于通过增强的抗原呈递和化学吸引两者获得的肿瘤抗原特异性T细胞免疫应答的增加，用编码与肿瘤抗原连接的IP-10的DNA进行疫苗接种对于治疗肿瘤具有很大的希望。
DNA vaccines have emerged as an attractive approach to generate antigen-specific T-cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1-polarizing chemokine, IP-10, to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, enhanced DNA vaccine potency. IP-10 linkage changed the location of E7 from the nucleus to the endoplasmic reticulum and led to the secretion of functionally chemoattractive chimeric IP-10/E7 protein. In addition, this linkage drastically enhanced the endogenous processing of E7 antigen through MHC class I. More importantly, we found that C57BL/6 mice intradermally vaccinated with IP-10/E7 DNA exhibited a dramatic increase in the number of E7-specific CD4(+) Th1 T-cells and CD8(+) T-cells and, consequently, were strongly resistant over the long term to E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. Thus, because of the increase in tumor antigen-specific T-cell immune responses obtained through both enhanced antigen presentation and chemoattraction, vaccination with DNA encoding IP-10 linked to a tumor antigen holds great promise for treating tumors.