Suradhat S, Yoo D, Babiuk L A, Griebel P, Baca-Estrada M E
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Viral Immunol. 1997;10(3):117-27.
Immunization with naked plasmid DNA effectively induces both humoral and cell-mediated immunity to vaccine antigens and can confer protection against numerous infectious diseases. To explore the potential use of DNA immunization to induce rotavirus-specific immune responses, we used plasmid DNA encoding the VP4 gene of bovine rotavirus (BRV). Intrasmuscular injection of the plasmid encoding the VP4 gene into C57BI/6 mice induced cell-mediated immunity as measured by cytokine production. Although DNA immunization did not induce a detectable BRV-specific antibody response, DNA-immunized animals were primed for antibody production and a cellular immune response. Following viral inoculation, the immunized animals displayed an enhanced number of BRV-specific antibody-secreting cells and cytotoxic activity. The immune response induced by DNA immunization alone or followed by viral inoculation was biased toward IFN-gamma production (Th1-like). CD4+ lymphocytes were the major source of IFN-gamma production in the spleen following DNA immunization. In contrast, a balanced cytokine production was observed in the spleens of animals receiving whole virus. These experiments showed that DNA immunization with a gene encoding the VP4 protein of BRV stimulated a Th1-like immune response in mice, and this bias in the immune response persisted following exposures to whole virus.
用裸露的质粒DNA进行免疫可有效诱导针对疫苗抗原的体液免疫和细胞介导免疫，并能提供针对多种传染病的保护。为了探索DNA免疫在诱导轮状病毒特异性免疫反应方面的潜在用途，我们使用了编码牛轮状病毒（BRV）VP4基因的质粒DNA。将编码VP4基因的质粒肌肉注射到C57BI/6小鼠体内，通过细胞因子产生来衡量，诱导了细胞介导免疫。尽管DNA免疫未诱导出可检测到的BRV特异性抗体反应，但经DNA免疫的动物已为抗体产生和细胞免疫反应做好了准备。在病毒接种后，免疫动物表现出BRV特异性抗体分泌细胞数量增加和细胞毒性活性增强。单独的DNA免疫或随后进行病毒接种所诱导的免疫反应倾向于产生IFN-γ（类似Th1型）。DNA免疫后，CD4+淋巴细胞是脾脏中IFN-γ产生的主要来源。相比之下，在接受全病毒的动物脾脏中观察到细胞因子产生较为平衡。这些实验表明，用编码BRV VP4蛋白的基因进行DNA免疫在小鼠中刺激了类似Th1型的免疫反应，并且在接触全病毒后这种免疫反应的偏向性仍然存在。
