| Co-Investigator(Kenkyū-buntansha) |
NOROSE Kazumi Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (30156244)
YANO Akihiko Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20135122)
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| Research Abstract |
We have attempted to develop DNA vaccine against toxoplasmosis targeting the professional antigen presenting cells (APC) such as Langerhans cells (LC) and dendritic cells (DC). As naive T cells can only be activated by the stimulation of professional APC, roles of LC/DC are crucial in inducing effective protective cellular immunities in host especially against intracellular parasitic diseases. DC reside within non-lymphoid tissues as immature cells and migrate to lymphoid tissues after receiving a maturation signal. Thus, DC possess a property of differentiation /maturation but not proliferation. Because of the property of non-proliferative cells, DNA transfection to DC has been very difficult. After struggling, we have decided to use a plasmid vector encoding bacterial CpG motifs. The synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs, i.e. ODN1466 and ODN1555, encoded in the plasmid vector, stimulate a strong innate immune response (PNAS, 93 : 2879, 1996 ; J. Immunol. 169 : 5590, 2002).
By using gene gun vaccination with this plasmid vector, we have analyzed the vaccine effects of Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) (a virulent tachyzoite-specific), T.g.HSP30 (a bradyzoite-specific) and SAG1 (a tachyzoite- specific) genes against toxoplasmosis. The vaccination with T.g.HSP70 gene induced the most prominent reduction in T. gondii loads in various organs of B6 and BALB/c mice at the acute and chronic phases of toxoplasmosis compared with T.g.HSP30 and SAG1 genes. A single gene gun vaccination with 2 μg of T.g.HSP70 gene induced a significant reduction in the number of T. gondii organisms compared with 50 μg of T.g.HSP70 gene vaccination by intramuscular or intraperitoneal injection. The vaccine effects of T.g.HSP70 gene persisted for more than 3 months. Thus, we have successfully established DNA vaccination method targeting LC/DC by using the gene gun (Vaccine, 2003 in press).
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