| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
After having completed our 2-year research activities, we established the following findings.
1.We have made the animal model of Trypanosoma cruzi infection as an experimental system exploring for vaccination strategies against intracellular infectious agents.
2.We demonstrated that the vaccination of mice with plasmid DNA encoding the trans-sialidase surface antigen (TSSA) protected only the B6 mice, but not other mouse strains, from lethal T.cruzi infection, and that the protective immunity is dependent on T cell immune responses.
3.We identified the H-2^b-restricted CD8^+ T cell epitope (ANYNFTLV) on TSSA, and therefore making the experimental system as useful for evaluating vaccine efficacy by measuring the immune responses against the epitope.
4.We found an interleukin-12 gene as effective genetic adjuvant for enhancing CD8^+ T cell immune response and protective immunity against T.cruzi infection.
5.We found that the activation of NK T cells by administering specific substance impaired the DNA vaccine-induced protective immunity against T.cruzi infection.
6.We demonstrated the critical roles of CD28-CD80/CD86 costimulatory pathway for inducing effective protective immune responses against T.cruzi infection.
7.We found, for the first time, the RANKL gene as a potent genetic adjuvant for enhancing CD8^+ T cell immune response and protective immunity against T.cruzi infection. CD40L and 4-1BBL genes were not effective for inducing similar efficacy in our experimental system.
8.We found the critical involvement of ICOS-B7RP1 costimulatory pathway in the regulation of immune responses against another intracellular parasitic protozoan, Leishmania major.
These results have clarified, at least partly, the optimal T cell vaccination strategy against intracellular infectious agents. Our efforts for defining effective T cell vaccines against intracellular infectious agent(s) will be continued further based on our findings presented above.
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