National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
J Immunol. 2011 Oct 1;187(7):3595-602. doi: 10.4049/jimmunol.1100043. Epub 2011 Aug 29.
Eimeria tenella, one of the seven species of chicken coccidia, elicits protective immunity against challenge infection with both homologous and heterologous strains. We endeavor to use recombinant E. tenella as a vaccine vehicle for expressing and delivering pathogen Ags and investigate immune responses against these foreign Ags. In this study, two lines of transgenic E. tenella expressing a model Ag, enhanced yellow fluorescent protein (EYFP), targeted to the micronemes and to the cytoplasm of the recombinant parasites were constructed to study the impact of Ag compartmentalization on immunogenicity. The MTT assay, intracellular cytokine staining, and real-time PCR were performed to detect the EYFP-specific proliferation and effector functions of splenic lymphocytes of immunized chickens. ELISA was used to measure anti-EYFP IgG and IgA responses. The results showed that both lines of transgenic parasites stimulated EYFP-specific lymphocyte proliferation and IFN-γ expression in CD4 and CD8 T cells, whereas a higher level of Ag-specific lymphocyte proliferation was elicited by the transgenic line expressing microneme-targeted EYFP. Furthermore, this line stimulated stronger IgA response than the one expressing cytoplasm-targeted EYFP after the second immunization. Our findings are encouraging for further investigation of the effect of Ag compartmentalization in transgenic Eimeria on immunogenicity and for the development of a eukaryotic vaccine vector using genetically modified Apicomplexa parasites.
柔嫩艾美耳球虫是鸡球虫的 7 个种之一,能激发针对同源和异源虫株攻毒感染的保护性免疫。我们努力使用重组柔嫩艾美耳球虫作为一种疫苗载体来表达和递呈病原体抗原,并研究针对这些外源抗原的免疫应答。在本研究中,构建了两条表达模式抗原增强型黄色荧光蛋白(EYFP)的转基因柔嫩艾美耳球虫系,EYFP 靶向微线体和重组虫体的细胞质,以研究抗原区室化对免疫原性的影响。通过 MTT 检测、细胞内细胞因子染色和实时 PCR 检测免疫鸡脾脏淋巴细胞中 EYFP 特异性增殖和效应功能。通过 ELISA 检测抗-EYFP IgG 和 IgA 应答。结果表明,两条转基因虫系均能刺激 CD4 和 CD8 T 细胞中 EYFP 特异性淋巴细胞增殖和 IFN-γ表达,而表达微线体靶向 EYFP 的转基因系能诱导更强的抗原特异性淋巴细胞增殖。此外,在第二次免疫后,该系能刺激更强的 IgA 应答。我们的研究结果为进一步研究转基因艾美耳球虫中抗原区室化对免疫原性的影响以及利用遗传修饰的顶复门寄生虫开发真核疫苗载体提供了令人鼓舞的信息。