| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
After having completed our 2-year research activities, we established the following findings.
(1) We have generated two recombinant viruses, recombinant adenovirus and recombinant vaccinia virus, which were inserted with a gene encoding the H-2^b-restricted CD8^+ T cell epitope (ANYNFTLV) identified on Trypanosoma cruzi trans-sialidase surface antigen (TSSA).
(2) We have demonstrated the immunogenicity of both recombinant viruses by detecting ANYNFTLV-specific CD8^+ T cells in splenocytes derived from virus-immunized B6 mice. However, the immunogenicity of both recombinant viruses was markedly different with regard to the level of CD8^+ T cell induction. Recombinant adenovirus was more efficient for priming the CD8^+ T cell responses.
(3) By performing the prime/boost immunization using TSSA-encoding DNA vaccine, recombinant adenovirus and recombinant vaccinia virus, we have demonstrated that the recombinant vaccinia virus was the best to exhibit maximal boosting capacity for the inductio
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n of ANYNFTLV-specific CD8^+ T cell responses.
(4) By increasing the immunizing doses of both recombinant viruses for prime/boost to 5 x 10^8 per head, the induction of ANYNFTLV-specific CD8^+ T cells has become better than the one induced by 5 x 10^7 per head-immunization.
(5) Considering that the RANKL (Ligand to receptor activator of NFκB) gene was effective as a genetic adjuvant for enhancing antigen-specific CD8^+ T cell responses, we have generated murine RANKL-expressing recombinant vaccinia virus. By coadministrating the RANKL-expressing recombinant vaccinia virus with ANYNFTLV-expressing recombinant viruses, we have demonstrated the enhanced induction of antigen-specific CD8^+ T cells.
(6) Mice immunized with ANYNFTLV-expressing recombinant viruses for prime/boost with RANKL-expressing recombinant vaccinia virus were completely protected from the lethal T.cruzi infection. We have demonstrated, for the first time that the immune responses against a single CD8^+ T cell epitope induced by virus vector vaccination was sufficient to confer protective immunity in experimental Chagas' disease.
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. Less
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