1998 Fiscal Year Annual Research Report

「マラリア原虫における寄生適応の分子生物学的解析」

Research Project

Project/Area Number	08281104
Research Institution	Osaka University
Principal Investigator	堀井俊宏大阪大学, 微生物病研究所, 助教授 (80142305)
Co-Investigator(Kenkyū-buntansha)	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) 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)
Keywords	マラリアワクチン / レコンビナントSERA蛋白 / Plasmodium falciparum / MSP-1遺伝子 / 遺伝子多型 / リスザル / ロプトリー / BCG
Research Abstract	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いう結果を得た(堀井)。このことはリコンビナントSE47'によって免疫を行なえば、防御抗体が誘導される可能性を強く示唆する。さらに、松岡がバキュロウイルスを用いたSERAの発現に成功し、太田がSERAヘルパーT細胞エピトープの解析を継続中である。MSP1を用いたワクチン開発の基礎研究としては、神原が、MSP1のブロック17をBCGと組あわせた組み替えBCGワクチンのマウスによる試験から、BCGの接種そのものによるIFN-gの産生がマウスに防御効果を与えることと、それにともなう原虫抗原に対するlgG2aの誘導がさらに防御免疫の効果を高めている事を示した。一方、田辺はタイから分離された69株の原虫のMSP1の遺伝的多型を解析し、MSP1分子のNー末端部とCー末端部の間に連鎖不均衡のあることを証明した。このことは特定のMSP1遺伝子型に何らかの選択圧が生じていることを意味する。裏出は熱帯熱マラ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、産生が原虫の膜分画で行われることを示した。松岡はバキュロウイルスを用いてPbs21に対するモノクローナル抗体の可変部の一本鎖抗体分子の発現を行ない、発現した13.1scFv分子による受動免疫によってオーシストの発育阻害を示した。この結果は、マラリア対策の一つであるTrasgenicmosquitの作製に極めて有望である・鳥居はメロゾイトが赤血球に侵入する際のロプトリー蛋白の役割を明らかにするため、メロゾイトの赤血球侵入像が観察される免疫電子顕微鏡資料の作製を試みている。この試みはメロゾイトの侵入機構を明らかにするうえで新しい研究の方向性であり、今後の展開に多いな期待が寄せられている。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] 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 in press.(1999)
[Publications] Sakai T.,Horii T.,Hisaeda H.,Zhang,et al.: "DNA immunization with plasmodium falciparum serine repeat antigen: Regulation of humoral immune response by coinoculation of cytokine expression plasmid." Parasitol.Int. in press.(1999)
[Publications] Brobey,R.K.B.,Iwakura,M.,Itoh,F.,Aso,K.,and Horii,T.: "Enzyme-inhibition system for identifying potential antimalarials that target highly drug-resistant mutants of Plasmodium falciparum dihydrofolate reductase." Parasitol.Int.47. 69-78 (1998)
[Publications] Pang X.-L. and Horii,T: "Complement-mediated killing of Plasmodium falciparum erythrocytic schizont with antibodies to the recombinant Serine Repeat Antigen(SERA)." Vaccine. 16. 1299-1305 (1998)
[Publications] Kokaze,A.,Miyadera,H.,Kita,K.,Machinami,R.et al.: "Phylogenetic identification of Sparganum proliferum as a Pseudophyllidean cestode." Parasitol.Int.46. 271-279. (1998)
[Publications] Ockenhouse,C.F.,et al.,: "Phase I/IIa safety,immunogenicity,and efficacy of NYVAC-Pf7,a pox-vectored,multiantigen,multistage caccine candidate for Plasmodium falciparum Malaria." J.Infect.Dis.177. 1664-1673 (1998)
[Publications] Kubata,B.K.,Eguchi,N.,Urade,Y.,et al.: "Plasmodium falciparum produces prostaglandins that are pyrogenic,somnogenic and immunosupressive substances in human." J.Exp.Med.188. 1197-1202 (1998)
[Publications] Ferreira,M.U.,Liu,Q.,Zhou,M.,Kimura,M.,et al.: "Stable pattem of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from southem Vietnam." J.Eukary.Microbiol.45. 131-136 (1998)
[Publications] Jongwutiwes,S.,Putaporntip,C.,Kanbara,H.and Tanabe,K.: "Variation in the thrombospond inrelated adhesive protein(TRAP)gene of Plasmodium falciparum from Thai field isolates." Mol.Biochem.Parasitol.92. 349-353 (1998)
[Publications] Ferreira,M.U.,Liu,Q.,Kaneko O.,Kimura,M.,Tanabe,K.et al.: "Allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from the southwestern Brazilian Amazon" Am.J.Trop.Med.Hyg.(in press). (1999)
[Publications] Yokoyama,D.,Saito-Ito,A.,Asao,N.,Tanabe,K.,et al.: "Modulation of the growth of Plasmodium falciparum in vitro by protein serine/threonine phosphatases." Biochem.Biophys.Res.Com.(in press). (1999)
[Publications] Ferreira,M.U.,Liu,Q.,Kimura,M.,Tanabe,K.and Kawamoto,F.: "Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple-clone Palsmodium falciparum infections in northem Tanzania." J.Parastiol. (in press). (1999)
[Publications] Cao,Y.-M.,Tsuboi,T.,Torii,M.: "Nitric oxide inhibits the development of Plasmodium yoelii gametecytes into gametes." Parasitol.Int.47. 157-166. (1998)
[Publications] Torii,M.and Aikawa,M.: "Ultrastructure of asexual stages." Malaria:Parasite biology,pathogenesis,and protection. Ed.by I.W.Sherman.A SM Press,Washington,D.C.123-134 (1998)
[Publications] Gao,Y.-M.,Tsuboi,T.,Liu,Y.-J.,Torii,T.: "Infected host serum blocks transmission of Plasmodium yoelii via a nitric oxide-dependent mechanism." Parasitol.Int.47. 225-224. (1998)
[Publications] Matsumoto,S.,Yukitake,H.,Kanbara,H.,Yamada,T.: "The recombinant BCG-secreting merozoite surface protein 1(MSP1)induces protection against rodent malaria parasites infection depending on MSP1-specific IFN-γ and parasites specific antibodies." J.Exp.Med.188. 845-854 (1998)
[Publications] Zhou,M.,Q.Liu,C.Wongsrichanalai,et al.: "High prevalence of Plasmodium malariae and P.ovale in malaria patients along the Thai-Myanmar border,as revealed by acridine orange staining and PCR-based diagnoses" Trop.Med.Int.Health. 3. 304-312 (1998)
[Publications] Yoshida A,Uchida YJ,Ishii A,Leafasia JL,Zhou D,et al.: "Polymorphism of the tumor necrosis factor A Gene in the Melanesian and Eeast-Asian populations." Immunogenetics. 47. 497-498 (1998)

1998 Fiscal Year Annual Research Report

「マラリア原虫における寄生適応の分子生物学的解析」

Principal Investigator

堀井 俊宏 大阪大学, 微生物病研究所, 助教授 (80142305)

Research Products

[Publications] 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 in press.(1999)

[Publications] Sakai T.,Horii T.,Hisaeda H.,Zhang,et al.: "DNA immunization with plasmodium falciparum serine repeat antigen: Regulation of humoral immune response by coinoculation of cytokine expression plasmid." Parasitol.Int. in press.(1999)

[Publications] Brobey,R.K.B.,Iwakura,M.,Itoh,F.,Aso,K.,and Horii,T.: "Enzyme-inhibition system for identifying potential antimalarials that target highly drug-resistant mutants of Plasmodium falciparum dihydrofolate reductase." Parasitol.Int.47. 69-78 (1998)

[Publications] Pang X.-L. and Horii,T: "Complement-mediated killing of Plasmodium falciparum erythrocytic schizont with antibodies to the recombinant Serine Repeat Antigen(SERA)." Vaccine. 16. 1299-1305 (1998)

[Publications] Kokaze,A.,Miyadera,H.,Kita,K.,Machinami,R.et al.: "Phylogenetic identification of Sparganum proliferum as a Pseudophyllidean cestode." Parasitol.Int.46. 271-279. (1998)

[Publications] Ockenhouse,C.F.,et al.,: "Phase I/IIa safety,immunogenicity,and efficacy of NYVAC-Pf7,a pox-vectored,multiantigen,multistage caccine candidate for Plasmodium falciparum Malaria." J.Infect.Dis.177. 1664-1673 (1998)

[Publications] Kubata,B.K.,Eguchi,N.,Urade,Y.,et al.: "Plasmodium falciparum produces prostaglandins that are pyrogenic,somnogenic and immunosupressive substances in human." J.Exp.Med.188. 1197-1202 (1998)

[Publications] Ferreira,M.U.,Liu,Q.,Zhou,M.,Kimura,M.,et al.: "Stable pattem of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from southem Vietnam." J.Eukary.Microbiol.45. 131-136 (1998)

[Publications] Jongwutiwes,S.,Putaporntip,C.,Kanbara,H.and Tanabe,K.: "Variation in the thrombospond inrelated adhesive protein(TRAP)gene of Plasmodium falciparum from Thai field isolates." Mol.Biochem.Parasitol.92. 349-353 (1998)

[Publications] Ferreira,M.U.,Liu,Q.,Kaneko O.,Kimura,M.,Tanabe,K.et al.: "Allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from the southwestern Brazilian Amazon" Am.J.Trop.Med.Hyg.(in press). (1999)

[Publications] Yokoyama,D.,Saito-Ito,A.,Asao,N.,Tanabe,K.,et al.: "Modulation of the growth of Plasmodium falciparum in vitro by protein serine/threonine phosphatases." Biochem.Biophys.Res.Com.(in press). (1999)

[Publications] Ferreira,M.U.,Liu,Q.,Kimura,M.,Tanabe,K.and Kawamoto,F.: "Allelic diversity in the merozoite surface protein-1 and epidemiology of multiple-clone Palsmodium falciparum infections in northem Tanzania." J.Parastiol. (in press). (1999)

[Publications] Cao,Y.-M.,Tsuboi,T.,Torii,M.: "Nitric oxide inhibits the development of Plasmodium yoelii gametecytes into gametes." Parasitol.Int.47. 157-166. (1998)

[Publications] Torii,M.and Aikawa,M.: "Ultrastructure of asexual stages." Malaria:Parasite biology,pathogenesis,and protection. Ed.by I.W.Sherman.A SM Press,Washington,D.C.123-134 (1998)

[Publications] Gao,Y.-M.,Tsuboi,T.,Liu,Y.-J.,Torii,T.: "Infected host serum blocks transmission of Plasmodium yoelii via a nitric oxide-dependent mechanism." Parasitol.Int.47. 225-224. (1998)

[Publications] Matsumoto,S.,Yukitake,H.,Kanbara,H.,Yamada,T.: "The recombinant BCG-secreting merozoite surface protein 1(MSP1)induces protection against rodent malaria parasites infection depending on MSP1-specific IFN-γ and parasites specific antibodies." J.Exp.Med.188. 845-854 (1998)

[Publications] Zhou,M.,Q.Liu,C.Wongsrichanalai,et al.: "High prevalence of Plasmodium malariae and P.ovale in malaria patients along the Thai-Myanmar border,as revealed by acridine orange staining and PCR-based diagnoses" Trop.Med.Int.Health. 3. 304-312 (1998)

[Publications] Yoshida A,Uchida YJ,Ishii A,Leafasia JL,Zhou D,et al.: "Polymorphism of the tumor necrosis factor A Gene in the Melanesian and Eeast-Asian populations." Immunogenetics. 47. 497-498 (1998)

堀井俊宏大阪大学, 微生物病研究所, 助教授 (80142305)