Developmental research of new generation DNA vaccine against microorganism using synthesized DNA

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In this study, we studied the importance of preventive DNA vaccine and virus vector vaccine against microbe infectious diseases. We constructed three types of DNA vaccine of pseudomonas containing Opr F/I, Pcr V and Pill genes. After immunization to mice with each or the combination of DNA vaccine, the mice were challenged with D1 strain. When immunized with the combination of three vaccines, more than 90% of the mice were survived. The preventive effect was high in order of Pcr V, OprF/I and Pili. Non immunized mice died 2 days later after challenging. Therefore, the vaccines which we constructed have strong effects to prevent infection and we confirmed that Pcr V worked as strong preventive antigen.On the other hand, to observe preventive effects against HIV-1, we developed a new DNA vector which the genes of Gag-Pal and Env were inserted into CAG promoter and an E1 deficient adeno 5/35 virus vector which the fiber of adeno virus type 5 replaced into the fiber of adeno type35. After immunization using these novel vaccines, we challenged monkeys with SHIV89.6. At the group which were immunized with DNA vaccine+Ad5/35, the viral load kept under the detectable level up to 25th weeks. Former adeno virus vector of type 5 had some faults such as liver obstacle. However, it became clear that Ad5/35 vector was best for human.From these results, we are going to develop more convenient immunizing route of pseudomonas vaccine for clinical trial. On HIV-1, we are planning to join with some pharmaceutical companies to do phase I clinical trial. Furthermore, we hope to develop other best DNA vaccines or virus vector vaccines against severe infectious diseases such as O-157 or Ave influenza using Ad5/35 vector.