延迟裂解型沙门菌递送新城疫mcDNA疫苗的免疫效应与机制研究

The vaccine design targeting Newcastle disease virus (NDV) genotype VII has been considered to be research hotspots recently, in which the DNA vaccine has drawn more and more attention due to its unique advantages, however, it is not appropriate for field application yet considering some drawbacks such as the injection immunization route. Regulated delayed lysis Salmonella has been designed to deliver protective antigens or DNA vaccine, which has been demonstrated to be effective in vaccine research for poultry necrotic enteritis..Minicircle DNA (mcDNA) contains only the components necessary for eukaryotic expression which makes it much better than plasmid DNA in vaccine research. In this study, we will take use of regulated delayed lysis Salmonella and mcDNA techniques to construct a mcDNA vaccine expressing F and HN proteins of genotype VII NDV. The immune response and protection against challenge will be determined to evaluate the efficiency of mcDNA vaccine in chicken. In addition, the underlying immunologic mechanisms will also be preliminary illuminated by measuring the differentiation of CD4+ and CD8+ T cells. This study will also build up a novel technique platform to take use of DNA vaccines in the control of animal disease.

针对基因VII型新城疫病毒(NDV)的疫苗设计是该领域近年来的研究热点，其中DNA疫苗因自身独特优势而倍受青睐，但受限于免疫途径等原因无法推广应用。延迟裂解型沙门菌可在机体内裂解并释放抗原或DNA疫苗，申请者前期已证明其可有效的用于禽坏死性肠炎疫苗研究。微环DNA (minicircle DNA, mcDNA) 仅包含真核表达必需序列，与质粒DNA相比在疫苗研究中更具优势。本研究拟将延迟裂解型沙门菌与mcDNA技术结合，构建共表达基因VII型NDV融合蛋白(F)、血凝素神经氨酸酶(HN)的mcDNA疫苗。免疫雏鸡后通过抗体水平检测及攻毒保护实验评价疫苗的免疫效应，并通过检测CD4+T细胞极化、CD8+T细胞类型转换等指标初步揭示新型mcDNA疫苗在雏鸡体内引起免疫反应的机制。本课题的研究成果将为建立一种新颖的利于在畜禽疫病防控中应用的mcDNA疫苗平台奠定基础。