| Project/Area Number |
05044168
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Osaka University |
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Principal Investigator |
HORII Toshihiro Osaka University, Research Institute for Microbial Diseases Associate Professor, 微生物病研究所, 助教授 (80142305)
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| Co-Investigator(Kenkyū-buntansha) |
ARMAH George ガーナ大学, 野口記念医学研究所, 研究主任
KRUNGKRAI Je チュラロンコン大学, 医学部, 助教授
BZIK David ダートマス大学, 医学部, 助教授
INSELBURG Jo ダートマス大学, 医学部, 教授
TAI Kumiko Osaka University, Research Institute for Microbial Diseases, Assistant, 微生物病研究所, 教務職員 (00187907)
MATAMURA Toshihide Osaka University, Research Institute for Microbial Diseases, Assistant, 微生物病研究所, 助手 (80268846)
MORIMATSU Katsumi Osaka University, Research Institute for Microbial Diseases, Assistant, 微生物病研究所, 助手 (70263308)
GEORGE Armah University of Ghana Research Chief
JERAPAN Krungkrai University of Chulalongkorn Associate Professor
DAVID Bzik Dartmouth Medical School Associate Professor
JOSEPH Inselburg Dartmouth Medical School Professor
杉山 智彦 大阪大学, 微生物病研究所, 助手 (90252709)
JERAPAN Krun チュラロンコン大学, 医学部・生化学教室(University of Chulal, 教授
BZIK David J ダートマス医科大学, 微生物講座(Dartmouth Medical School, 助教授
ARMAH Geroge ガーナ大学, 野口記念医学研究所(University of Ghana,Nogu, 研究主任
INSELBURG J ダートマス医科大学, 微生物講座(Dartmouth Medical School, 教授
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1993: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Plasmodium falciparun / Malaria vaccine / SERA / Antigenic variation / Codon frequency / Synthetic gene / Epitope mapping / 三日熱マラリア / ワクチン / 合成遺伝子 / SERA蛋白質 / マラリア抗原 |
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| Research Abstract |
SERA (serine repeat antigen, 113 kDa) is a parasitophorous vacuole antigen of Plasmodium falciparum. SERA protein that cross-reacts with IgG in human plasma from an endemic area and with a monoclonal antibody inhibitory against the parasite growth in vitro. For developing malaria vaccine, we have developed the expression system of recombinant SERA proteins in E.coli by constructing the synthetic genes with the altered codon usage. We have constructed synthetic genes covering three parts of SERA including N-terminal domain with 47 kDa, central domain with 23 kDa and C-terminal domain with (Sugiyama et al., in press).
When mice or rats were immunized with SE47' protein that is one of the recombinant products encoding 17-382 amino acid residues of SERA (N-terminal domain), the growth inhibitory anti-sera against the cultural parasites were induced. The most inhibitory anti-sera was obtained when the animals were immunized with SDS-denatured SE47' protein without any adjuvants. This observation suggests that the primary structure of SE47' protein corresponds to the induction of growth inhibitory antibodies. Since the protein tends to aggregate in the aqueous solution, the hydrophobic interaction of intra or inter molecules might mask the effective presentation of the critical region to the host immune system. We suppose that the Freund's adjuvant may have a hydrophobic interaction with SE47' protein (Sugiyama et al., ibid).
SERA gene is thought to be well conserved among the isolated strains, however, we found that the amino acid changes are more often occurred in the N-terminal region that induce protective antibody than the other parts of gene. The protective immunity developed against the N-terminal region may accelerate the evolution speed in the region (Morimatsu, Horii et al., in preparation).
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