Study on the DNA immunization against microbial infection

为了开发针对微生物感染如HIV-1的强有力的DNA疫苗，我们用我们开发的DNA疫苗免疫小鼠、日本猕猴和其他实验动物。DNA疫苗经鼻内或皮肤涂敷免疫小鼠3次后，均能诱导产生较强的HIV-1特异性抗体和细胞免疫应答。将DNA疫苗与IL-2和GM-CSF表达质粒共同给药，分别显著增加Th 1和Th 2免疫应答。本实验室制备的表达HIV-1 C进化枝包膜蛋白和gag-pol蛋白的DNA疫苗已通过Karolinska研究所的鉴定。用HIV-1和SIV嵌合病毒（SHIV）攻击获得HIV-1免疫应答和部分感染保护。HIV C基因疫苗正在进行I期临床试验。另一方面，表达HIV-1进化枝E包膜蛋白和gag-pol蛋白的DNA疫苗也在动物模型中诱导了强烈的免疫应答。在另一个项目中，我们用表达流感病毒M蛋白的CMV启动子调控的流感病毒DNA疫苗免疫小鼠。用同种和异种流感病毒攻击免疫小鼠。结果表明，流感DNA疫苗不仅能抵抗同种流感病毒的攻击，而且能抵抗异种流感病毒的感染。现在，我们正在雪貂模型中测试DNA疫苗。此外，DNA疫苗与含有20个拷贝的CpG基序的DNA质粒共同施用显著增加抗原特异性细胞介导的免疫。含CpG基序的DNA疫苗有望用于下一代DNA疫苗的研究。综上所述，上述国际合作非常重要。

To develop powerful DNA vaccines against microorganism infection such as HIV-1, we immunized mice, Japanese macaque monkeys and other experimental animals with our developed DNA vaccines. Their immune responses and protective ability against microorganisms were examined.After the mice were immunized 3 times with DNA vaccine by intranasal or skin painting route, the HIV-1-specifical antibody and cell-mediated immune response were strongly induced. Co-administration of the DNA vaccine with IL-2 and GM-CSF expression plasmids greatly increased Th1 and Th2 immune responses, respectively. A DNA vaccine expressing HIV-1 clade C envelope protein and gag-pol protein prepared in our lab has been examined by Karolinska Institute. The HIV-1-immune response and partially infectious protection challenged with an HIV-1 and SIV chimera virus (SHIV) were obtained. The HIV clade C DNA vaccine is being tested for phase I trial. On the other hand, a DNA vaccine expressing HIV-1 clade E envelope protein and gag-pol protein also induced strong immune response in animal models. Now the DNA vaccine has been ready for phase I trial.In another project, we immunized mice with influenza DNA vaccine expressing influenza M protein under the control of CMV promoter. The immunized mice were challenged with homogeneous and heterogeneous influenza virus. Our results revealed that the influenza DNA vaccine not only protected from homogeneous influenza virus challenge, but also from heterogeneous influenza virus infection. Now, we are testing the DNA vaccine in a ferret model. Furthermore, co-administration of DNA vaccine with a DNA plasmid containing 20 copies of CpG motif significantly increased antigen specific cell-mediated immunity. We will use the DNA vaccine containing CpG motif in our next generation DNA vaccine. Taken together, the international cooperation described above is very important.