Lin T, Liang S, Meng F, Han Q, Guo C, Sun L, Chen Y, Liu Z, Yu Z, Xie H, Ding J, Fan D
State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China.
Clin Exp Immunol. 2006 May;144(2):319-25. doi: 10.1111/j.1365-2249.2006.03065.x.
MG7-Ag, gastric cancer-associated antigen, has been shown to be immunogenic and has been used as marker molecule for prognosis. In a previous study, we developed an oral DNA vaccine based on MG7-Ag mimotope. However, we failed to detect cellular immune response using the oral MG7-Ag mimotope DNA vaccine. To induce significant T cell response, we developed a recombinant adenovirus vaccine based on MG7-Ag mimotope and evaluated the efficacy and protective effects of heterologous prime-boost immunization protocol with an oral DNA vaccine previously developed. We found that both vaccines were able to elicit a significant humoral response against MG7-Ag, while the highest serum titre MG7 antibody was detected in mice immunized with the heterologous prime-boost immunization protocol. Enzyme-linked immunospot (ELISPOT) assay demonstrated that the heterologous prime-boost immunization strategy was more efficient in inducing T cell response than the homologous prime-boost strategy. In the tumour challenge assay, 2 of 5 mice immunized with the heterologous prime-boost protocol were tumour free, while none of the mice in homologous prime-boost groups or control groups was tumour free. Those tumour-bearing mice in the heterologous prime-boost regime had smaller tumour masses than their counterparts in the homologous prime-boost groups or control groups. Therefore, our study suggests that vaccines against MG7-Ag induce significant immune response against gastric cancer, and that the heterologous prime-boost protocol using different types of vaccines could achieve better protective effect than the homologous prime-boost protocol.
MG7抗原,即胃癌相关抗原,已被证明具有免疫原性,并已用作预后的标志物分子。在先前的一项研究中,我们开发了一种基于MG7抗原模拟表位的口服DNA疫苗。然而,我们未能使用口服MG7抗原模拟表位DNA疫苗检测到细胞免疫反应。为了诱导显著的T细胞反应,我们开发了一种基于MG7抗原模拟表位的重组腺病毒疫苗,并评估了先前开发的口服DNA疫苗进行异源初免-加强免疫方案的疗效和保护作用。我们发现两种疫苗都能够引发针对MG7抗原的显著体液反应,而异源初免-加强免疫方案免疫的小鼠中检测到最高的血清滴度MG7抗体。酶联免疫斑点(ELISPOT)分析表明,异源初免-加强免疫策略在诱导T细胞反应方面比同源初免-加强策略更有效。在肿瘤攻击试验中,5只接受异源初免-加强方案免疫的小鼠中有2只无肿瘤,而同源初免-加强组或对照组的小鼠均无肿瘤。异源初免-加强方案中的荷瘤小鼠的肿瘤块比同源初免-加强组或对照组中的荷瘤小鼠更小。因此,我们的研究表明,针对MG7抗原的疫苗可诱导针对胃癌的显著免疫反应,并且使用不同类型疫苗的异源初免-加强方案比同源初免-加强方案可实现更好的保护效果。