1999 年度実績報告書

「マラリア原虫における寄生適応の分子生物学的解析」

研究課題

研究課題/領域番号	08281104
研究機関	大阪大学
研究代表者	堀井俊宏大阪大学, 微生物病研究所, 教授 (80142305)
研究分担者	神原廣二長崎大学, 熱帯医学研究所, 教授 (20029789) 鳥居本美愛媛大学, 医学部, 教授 (20164072) 田辺和裄大阪工業大学, 工学部, 教授 (40047410) 裏出良博大阪バイオサイエンス研究所, 部長 (10201360) 松岡裕之自治医科大学, 医学部, 助教授 (10173816)
キーワード	マラリアワクチン / SERA / Plasmodium falciparum / MSP-1 / BCG / ロプトリー / プロスタグランジン / HLA-DR
研究概要	リコンビナントSERA(SE47')によるワクチン開発では、流行地域の児童におけるlgGサブクラスごとの抗SE47'抗体価の測定とマラリア症状との関係についての解析し、ウガンダの高度マラリア流行地域において抗SE47'lgG3の抗体価が高い児童はマラリアによる発熱が認められないとともに、血中の原虫数が有意に低いという結果を得た。さらに、精製したヒト抗SE47'lgG3はマラリア原虫の増殖を阻害した。これらの結果はリコンビナントSE47'がマラリアワクチンとして実用可能であること強く支持する(堀井)。松岡はP.bergheiCSP遺伝子を遺伝子銃によって直接マウスの肝臓に打ち込むことにより高い感染防御効果を誘導した。また、太田はHLA-DRに結合するSE47'上のアミノ酸配列を同定した。MSP1を用いたワクチン開発の基礎研究としてこれまで組み替えBCGワクチンの有効性をマウスによる試験から示してきたが、ヒトマラリアワクチンの開発に向けた基礎研究の基盤を作った。マラリア原虫の寄生適応に関する研究として、田辺はMSP1の遺伝的多型において連鎖不均衡のあることを証明したが、これが免疫学的選択と同時に流行の突発にも関連していることを示した。鳥居はメロゾイトが赤血球に侵入する際に重要な役割を果たしているロプトリー蛋白遺伝子のクローニングをネズミマラリア原虫を用いて行い、さらにその機能解析を進めた。裏出は熱帯熱マフリア原虫によるプロスタグランデインの産生について、その産生機構を生化学的に分析をし、ヘモゾインの関与がないことを証明し、さらに熱にも安定な分画に活性が回収されることを示した。

研究成果

(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] Sakai T., Horii T., Himeno K., et al.: "DNA immunization with Plasmodium falciparum serine repeat antigen : Regulation of humoral immune response by coinoculation of cytokine expression plasmid"Parasitology International. 48. 27-33 (1999)
[文献書誌] Pang X.-L. Mitamura T. and Horii T.: "Antibodies specific to N-terminal domain of Plasmodium falciparum serine repeat antigen (SERA) agglutinate merozoites and schizonts"Infection and Immunity. 22. 1321-1327 (1999)
[文献書誌] Kim H. S., Horii T., et al.: "Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent"Biol. Pharm. Bull.. 22. 532-534 (1999)
[文献書誌] Wang P., Brogey R. K. B., Horii T., Sims P. F. G. and Hyde J. E.: "Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy"Molecular Microbiology. 32. 1254-1262 (1999)
[文献書誌] Belperron, A. A., Feltquate, D., Fox, B. A., Horii T. and Bzik D. J.: "Immune responses induced by gene gun or intramuscular infection of DNA vaccines that express immunogenic regions of the Serine Repeat Antigen from Plasmodium falciparum"Infection and Immunity. 67. 5163-5169 (1999)
[文献書誌] S. He, A. Saito-Ito, K. Tanabe and T. Matsumura: "Plasmodium falciparum : effective use of the CO_2-NaHCO_3 buffere system for evaluating chloroquine resistance"Experimental Parasitology. (in press). (2000)
[文献書誌] J. Fu, K. Tanabe, N. Ohta, et al.: "Epitope-specific impairment of antibody production to MSP1 of Plasmodium falciparum in symptomatic patients with malaria"Parasitology Research. (in press). (2000)
[文献書誌] S. Takeo, K. Tanabe et al.: "Succinate dehydrogenase in Plasmodium falciparum mitochondria : Molecular characterization of the SDHB genes for the catalyticsubunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits"Molecular and Biochemkical Parasitology. (in press). (2000)
[文献書誌] M. Kimura, K. Tanabe, et al.: "Gametocyte-dominant expression of a novel type ATPase in Plasmodium yoelii"Molecular and Biochemical Parasitology. 104. 331-336 (1999)
[文献書誌] K. Tanabe et al.: "Selection and genetic drift of polymorphisms within the merozoite surface protein-1 gene of Plasmodium falciparum"Gene. 241. 325-331 (2000)
[文献書誌] L. A. Da Silva, K. Tanabe, et al.: "Allelic diversity and antibody revognition of Plasmodium merozoite surface protein-1 under hypoendemic malaria transmission in the Brazilian Amazon"Infection and Immunity. 67. 5906-5916 (1999)
[文献書誌] Y. Hirano, K. Tanabe, M. Oka and T. Hayashi: "Theoretical conformational analysis on model polypeptides of merozoite surface antigen"Reports on Progress in Polymer Physics in Japan. 41. 575-578 (1999)
[文献書誌] Matsumoto S., Yukitake H., Kanbara H. & Yamada T.: "Long-lasting protective immunity against rodent malaria parasite infection at the blood stage by recombinant BCG secreting merozoite surface protein 1"Vaccine. 13. 332-334 (2000)
[文献書誌] Luo, E., H. Matsuoka, et al.: "Changes of salivary proteins during feeding and detection of saliva proteins in the midgut after feeding in a malaria vector mosquito, Anopheles stephensi (Diptera : Culicidae)"Medical Entomology and Zoology. (in press). (2000)
[文献書誌] Yoshida, S., H. Matsuoka.a, et al.: "A single-chain antibody fragment specific for the Plasmodium berghei ookinete protein Pbs21 confers transmission blockade in the mosquito midgut"Molecular and Biochemical Parasitology. 104. 195-204 (1999)
[文献書誌] Fu, J., Matsuoka H., Chinzei Y. & Ohta N. et al.: "A simple screening method detecting bindings between oligopeptides and HLA-DR molecules on filter papers : Possible application for mapping of putative helper T cell epitopes on MSP1 of Plasmodium falciparum"Microbiological Immunology. (in press). (2000)
[文献書誌] Fu, J., J. Matsuoka et al.: "Epitope-specific impaiment of antibody production to MSP1 of Plasmodium falciparum in symptomatic patients with malaria"Parasitology Research. (in press). (2000)
[文献書誌] Tantular, I. S., H. Matsuoka, et al.: "Field trials of a rapid test for G6PD deficiency in combination with a rapid diagnosis of malaria"Tropical medicine and International Health. 4. 245-250 (1999)
[文献書誌] Ando K., Matsuoka H., Chizei Y et al.: "Sporozoite in version of Plasmodium berghei, rodent malaria parasite, to the salivary glands of the vector mosquito, Anopheles stephensi : An electromicroscopic study"Jpn Trop med Hyg. 27. 7-12 (1999)
[文献書誌] Yoshida A, Himeno K & Ohta N., et al.: "Schistosoma mansoni infection cancels the suceptibility to Plasmodium chabaudi through induction of Th1-dominant circumstances in the susceptible A/J mice"International Immunology. (in press). (2000)
[文献書誌] Zhang, M., Hisaeda, H., Tsuboi, T., Torii, M., Sakai, T., Himeno, K., et al.: "Stage specific expression of heat shock protein 90 in murune malaria parasite Plasmodium yoelii"Experimental Parasitology. 93. 61-65 (1999)

1999 年度 実績報告書

「マラリア原虫における寄生適応の分子生物学的解析」

研究代表者

堀井 俊宏 大阪大学, 微生物病研究所, 教授 (80142305)

研究成果

[文献書誌] Sakai T., Horii T., Himeno K., et al.: "DNA immunization with Plasmodium falciparum serine repeat antigen : Regulation of humoral immune response by coinoculation of cytokine expression plasmid"Parasitology International. 48. 27-33 (1999)

[文献書誌] Pang X.-L. Mitamura T. and Horii T.: "Antibodies specific to N-terminal domain of Plasmodium falciparum serine repeat antigen (SERA) agglutinate merozoites and schizonts"Infection and Immunity. 22. 1321-1327 (1999)

[文献書誌] Kim H. S., Horii T., et al.: "Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent"Biol. Pharm. Bull.. 22. 532-534 (1999)

[文献書誌] Wang P., Brogey R. K. B., Horii T., Sims P. F. G. and Hyde J. E.: "Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy"Molecular Microbiology. 32. 1254-1262 (1999)

[文献書誌] Belperron, A. A., Feltquate, D., Fox, B. A., Horii T. and Bzik D. J.: "Immune responses induced by gene gun or intramuscular infection of DNA vaccines that express immunogenic regions of the Serine Repeat Antigen from Plasmodium falciparum"Infection and Immunity. 67. 5163-5169 (1999)

[文献書誌] S. He, A. Saito-Ito, K. Tanabe and T. Matsumura: "Plasmodium falciparum : effective use of the CO_2-NaHCO_3 buffere system for evaluating chloroquine resistance"Experimental Parasitology. (in press). (2000)

[文献書誌] J. Fu, K. Tanabe, N. Ohta, et al.: "Epitope-specific impairment of antibody production to MSP1 of Plasmodium falciparum in symptomatic patients with malaria"Parasitology Research. (in press). (2000)

[文献書誌] S. Takeo, K. Tanabe et al.: "Succinate dehydrogenase in Plasmodium falciparum mitochondria : Molecular characterization of the SDHB genes for the catalyticsubunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits"Molecular and Biochemkical Parasitology. (in press). (2000)

[文献書誌] M. Kimura, K. Tanabe, et al.: "Gametocyte-dominant expression of a novel type ATPase in Plasmodium yoelii"Molecular and Biochemical Parasitology. 104. 331-336 (1999)

[文献書誌] K. Tanabe et al.: "Selection and genetic drift of polymorphisms within the merozoite surface protein-1 gene of Plasmodium falciparum"Gene. 241. 325-331 (2000)

[文献書誌] L. A. Da Silva, K. Tanabe, et al.: "Allelic diversity and antibody revognition of Plasmodium merozoite surface protein-1 under hypoendemic malaria transmission in the Brazilian Amazon"Infection and Immunity. 67. 5906-5916 (1999)

[文献書誌] Y. Hirano, K. Tanabe, M. Oka and T. Hayashi: "Theoretical conformational analysis on model polypeptides of merozoite surface antigen"Reports on Progress in Polymer Physics in Japan. 41. 575-578 (1999)

[文献書誌] Matsumoto S., Yukitake H., Kanbara H. & Yamada T.: "Long-lasting protective immunity against rodent malaria parasite infection at the blood stage by recombinant BCG secreting merozoite surface protein 1"Vaccine. 13. 332-334 (2000)

[文献書誌] Luo, E., H. Matsuoka, et al.: "Changes of salivary proteins during feeding and detection of saliva proteins in the midgut after feeding in a malaria vector mosquito, Anopheles stephensi (Diptera : Culicidae)"Medical Entomology and Zoology. (in press). (2000)

[文献書誌] Yoshida, S., H. Matsuoka.a, et al.: "A single-chain antibody fragment specific for the Plasmodium berghei ookinete protein Pbs21 confers transmission blockade in the mosquito midgut"Molecular and Biochemical Parasitology. 104. 195-204 (1999)

[文献書誌] Fu, J., J. Matsuoka et al.: "Epitope-specific impaiment of antibody production to MSP1 of Plasmodium falciparum in symptomatic patients with malaria"Parasitology Research. (in press). (2000)

[文献書誌] Tantular, I. S., H. Matsuoka, et al.: "Field trials of a rapid test for G6PD deficiency in combination with a rapid diagnosis of malaria"Tropical medicine and International Health. 4. 245-250 (1999)

[文献書誌] Ando K., Matsuoka H., Chizei Y et al.: "Sporozoite in version of Plasmodium berghei, rodent malaria parasite, to the salivary glands of the vector mosquito, Anopheles stephensi : An electromicroscopic study"Jpn Trop med Hyg. 27. 7-12 (1999)

[文献書誌] Yoshida A, Himeno K & Ohta N., et al.: "Schistosoma mansoni infection cancels the suceptibility to Plasmodium chabaudi through induction of Th1-dominant circumstances in the susceptible A/J mice"International Immunology. (in press). (2000)

[文献書誌] Zhang, M., Hisaeda, H., Tsuboi, T., Torii, M., Sakai, T., Himeno, K., et al.: "Stage specific expression of heat shock protein 90 in murune malaria parasite Plasmodium yoelii"Experimental Parasitology. 93. 61-65 (1999)

1999 年度実績報告書

堀井俊宏大阪大学, 微生物病研究所, 教授 (80142305)