Study on the DNA immunization against microbial infection

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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.