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Field evaluation of vaccine candidates against schistosomiasis japonica and molecular analysis of vaccine efficacy

Research Project

Project/Area Number 12576009
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field 寄生虫学(含医用動物学)
Research InstitutionNagoya City University

Principal Investigator

OHTA Nobuo  Nagoya City University, Graduate School of Medical Sciences, Professor and Chair, 大学院・医学研究科, 教授 (10143611)

Co-Investigator(Kenkyū-buntansha) HIRAYAMA Kenji  Nagoya City University institute of Tropical Medicine, Professor and Chair, 熱帯医学研究所, 教授 (60189868)
SUZUKI Takashi  Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (70305530)
MARUYAMA Haruhiko  Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (90229625)
NARA Takeshi  Juntendo University, School of Medicine, Research Associate, 医学部, 助手 (40276473)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2002: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2001: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsSchistosoma japonicum / calpain / vaccine / DNA vaccine / CpG oligonucleotides / cercaria / Immunohistostaining / 日本住血虫 / パラミオシン / GST融合タンパク / 感染防御 / 虫卵肉芽腫 / アジュバント / サイトカイン
Research Abstract

In the year of 2002, we prepared a large amount of recombinant protein of calpain of Schistosoma japonicum, and by the use of the recombinant protein, we produced monoclonal antibodies to S.japonicum calpain and also tested their vaccine effects in pigs. Immunohistochemistry using our mAbs revealed tissue distribution and changes of expression in developmental stages in S.japonicum. We observed strong signal in the excretory grand of cercariae. This seemed to explain a probable explanation of vaccine efficacy of calpain. In our pig trials, we observed significant reduction in egg production, however, no reduction in worm burden occurred. Durning experimental infection in pigs, there was no booster effect for antibody production to calpain, and this might explain not so good effects as were observed for paramyosin in pig trials. DNA vaccination was also investigated. As a rout of DNA inoculation, intradermal injection at ear pad induced strong antibody production. In our previous results, Th1-dominant responses seem to be important for vaccine effects. In line with this, we tested effects of CpG oligonucleotides in protective immunity to S.japonicum. Mice treated with CpG induced strong Th1 responses and significant reduction in egg granuloma formation in the liver. Intranasal treatment of CpG also induced strong effects comparable to those by intramuscular injection. Considering short half-life of CpG in vivo, repeated treatment is needed. Our intranasal treatment as a non-invasive inoculation is good for repeated treatment of CpG. As a cooperative research with Chinese counterparts, we made progress of calpain vaccine for schistosomiasis japonica, and the near future prospect has been fixed in our research project.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Zhang R, Takahashi S, Maruyama H, Yoshida A, Yabu Y, Shirai T, Ohta N.: "Cloning and molecular characterization of calpain, a calcium-activated neutral proteinase, from different strains of Schistosoma japonicum"Parasitol Int. 48. 233-242 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chen H, Nara T, Zeng X, Satoh M, Wu G, Kojima S, Zhang Z, Hirayama K.: "Vaccination of domestic pig with recombinant paramyosin against Schistosoma japonicum in China"Vaccine. 14. 2142-2146 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fu J, Hato M, Igarashi K, Suzuki T, Matsuoka H, Ishii A, Leafasia JL, Chinzei Y, Ohta N.: "A simple screening method detecting bindings between oligopeptides and HLA-DR"Microbiology and Immunology. 44. 249-257 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A, Mruyama H, Kumagai T, Amano T, Kobayasi F, Zhang M, Himeno, Ohta N.: "Schistosoma mansoni infection cancels the susceptibility to Plasmodium chabaudi through induction of Th1-dominant circumstances in the susceptible A/J mice"International Immunology. 12. 1117-1125 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama H, Osada Y, Yoshida A, Futakuchi M, Kawaguchi H, Zhang R. Fu J, Shirai T, Kojima S, Ohta N.: "Protective mechanisms against the intestinal nematode, in Strongyloides venezuelensis, in Schistosoma japonicum-infected mice"Parasite Immunology. 22. 279-286 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 太田伸生, 吉田彩子: "寄生虫と生体防御"Biotherapy. 14. 597-602 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang R, Yoshida A, Kumagai T, Kawaguchi H.Maruyama H, Suzuki T, Itoh M, El-Malky M, Ohta N.: "Vaccination with calpain induces a Th1-biased protective immune response against Schistosoma japonicum"Infection and Immunity. 69. 386-391 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] He H, Zhang R, Kawaguchi H, Itoh M, Chen Y, Ohta N.: "Role of testosterone in host-parasite interaction during murine experimental infection of Schistosoma japonicum"Japanese Journal of Tropical Medicine. 29. 1-4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okumura-Noji K, Sasai K, Zhang R, Kawaguchi H, Maruyama H, Tada T, Takahashi H, Okazaki M, Miida T, Sakuma N, Kimura G, Ohta N, Yokoyama S.: "Cholesteryl ester transfer protein-deficiency causes slow egg embryonation of Schistosoma japonicum"Biochemical Biophysical Research Communications. 286. 305-310 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirayama K.: "Immunogenetic analysis of severe forms of parasitic diseases"Acta Medica Nagasakiensia. 46. 1-5 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osada Y, Janecharut T, Hata H, Mahakunkijcharoen Y, Chen XW, Nara T, Kita K, Kojima S.: "Protective immunity to Schistosoma japonicum infection depends on the balance of T helper cytokine responses in mice vaccinated with γ-irradiated cercariae"Parasite Immunology. 23. 251-258 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A, Maruyama H, Kumagai T, Amano T, Kobayashi F, Kuribayashi K, Ohta N.: "Enhanced UV♀1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses"Parasitology International. 51. 177-186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirayama K.: "Genetic factors associayed with development of cerebral malaria and fibrotic schistosomiasis"Korean Journal of Parasitology. 40. 165-172 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 平山謙二: "感染症の遺伝解析"医学のあゆみ. 202. 877-882 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai T, El-Malky M, Maruyama H, Ohta N.: "Effects of CpG oligo-nucleotides on Schistosoma japonicum infection in mice"Nagoya Medical Journal. 46. 99-110 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itoh M, Ohta N, Kanazawa T, Nakajima Y, Sho M, Minami M Zhou D, Chen Y, He H, He Y, Zhong Z.: "Sensitive enzyme-linked immunosorbent assay with urine samples : A tool for surveillance of schistosomiasis japonica"Southeeast Asian Journal of Tropical Medicine and Hygiene. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai K, Maruyama H, Hato M, Ohmae H, Ohta N.: "A comparative study on localization of calpain in the adult worms and cercariae of Schistosoma japonicum and Schistosoma mansoni"(投稿中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 太田伸生: "看護のための最新医学講座第4巻"中山書店. 3 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 太田伸生: "今日の治療指針2002"医学書院. 1 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang R., Takahashi S., Maruyama H., Yoshida A., Yabu Y., Shirai T., & Ohta N.: "Cloning and molecular characterization of calpain, a calcium-activated neutral proteinase, from different strains of Schistosoma japonicum"Parasitology International. 48. 233-242 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chen H., Nara T., Zeng X., Satoh M., Wu G., Kojima S., Zhang Z., & Hirayama K.: "Vaccination of domestic pig with recombinant paramyosin against Schistosoma japonicum in China"Vaccine. 14. 2142-2146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fu J., Hato M., Igarashi K., Suzuka T., Matsuoka H., Ishii A., Leafasia JL., Chinzei Y., & Ohtani N.: "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"Microbiology and Immunology. 44. 249-257 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A., Maruyama H., Kumagai T., Amano T., Kobayashi F., Zhang M., Himeno., & Ohta N.: "Schistosoma mansoni infection cancels the susceptibility to Plasmodium chabaudi through induction of Th1-dominant circumstances in the susceptible A/J mice"International Immunology. 12. 1117-1125 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama H., Osada Y., Yoshida A., Futakuchi M., Kawaguchi H., Zhang R., Fu J., Shirai T., Kojima S., & Ohta N.: "Protective mechanisms against the intestinal nematode, Strongyloides venezuelensis, in Schistosoma japonicum-infected mice"Parasite Immunology. 22. 279-286 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta N., & Yoshida A..: "Parasitic infection and biodefence"Biotherapy. 14. 597-602 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang R., Yoshida A., Kumagai T., Kawaguchi H., Maruyama H., Suzuki T., Itoh M., El-Malky M., & Ota N.: "Vaccination with calpain induces a Th1-biased protective immune response against Schisto soma japonicum"Infection and Immunity. 69. 386-391 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] He H., Zhang R., Kawaguchi H., Itoh M., Chen Y., Chen Y., & ohta N.: "Role of testosterone in host-parasite interaction during murine experimental infection of Schistosoma japonicum"Japanese Journal of Tropical Medicine. 29. 1-4 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okumura-Noji K., Sasai K., Zhang R., Kawaguchi H., Maruyama H., Tada T., Takahashi H., Okazaki M., Miida T., Sakuma N., Kimura G., Ohta N., & Yokoyama S.: "Cholesteryl ester transfer protein-Scistosoma japonicum"Biochemical Biophysical Research Communications. 286. 305-310 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirayama K.: "Immunogenetic analysis of severe forms of parasitic diseases"Acta Medica Nagasakiensia. 46. 1-5 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osada Y., Janecharut T., Hata H., Mahakunkijcharoen Y., Chen XW., Nara T., Kita K., & Kojima S.: "Protective immunity to Schistosoma japonicum infection depends on the balance of Thelper cytokine responses in mice vaccinated with γ-irradiated cercariae"Parasite Immunology. 23. 251-258 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A., Maruyama H., Kumagai T., Amano T., Kobayashi F., Kuribayashi K., & Ohta N.,: "Enhanced UV ♀1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses"Parasitology International. 51. 177-186 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirayama K.: "Genetic factors associayed with development of cerebral malaria and fibrotic schistosomiasis"Korean Journal of Parasitology. 40. 165-172 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirayama K.: "Genetics of Infectious diseases"Igaku no Ayumi. 202. 877-882 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai T., El-Malky M., Maruyama H., & Ohta N.: "Effects of CpG oligo-nucleotides on Schistosoma japonicum infection in mice"Nagoya Medical Journal. 46. 99-110 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itoh M., Ohta N., Kanazawa T., Nakajima Y., Sho M., Minai M., Zhou D., Chen Y., He H., He Y., & Zhong Z.: "Sensitive enzyme-linked immunosorbent assay with urine samples: A tool for surveillance of schistosomiasis japonica"Southeeast Asian Journal of Tropical medicine and Hygiene, (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai K., Maruyama H., Hato M., Ohmae H., & Ohta N.: "A comparative study on localization of calpain in the adult worms and cercariae of Schistosoma japonicum and Schistosoma mansoni"Submitted.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta N.: "Symphonia Medica Nursing"Nakayama Shoten. 4:3 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta N.: "Today's Therapy 2002"Igaku Shoin. 2002:1 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida A, Maruyama H, Kumagai T, Amano T, Kobayashi F, Kuribayashi K, Ohta: "Enhanced UV ♀1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses"Parasitol Int. 51. 177-186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kumagai T, El-Malky M, Maruyam H, Ohta N.: "Effects of CpG oligonucleorides on Schistosoma japonicum infection in mice"Nagoya Med J. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Itoh M, Ohta N, Kanazawa T, Nakajiam Y, Sho M, Minai M, Zhou D, Chen Y, He H, He Y, Zhong Z: "Sensitive enzyme-linked immunosorbent assay with urine samles : A tool for surveillance of schistosomiasis japonica"Southeast Asian J Trop Med. Pub Health. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama H, Hirabayashi Y, El-Malky M, Okamura S, Aoki M, Itagaki T, Nakamura-Uchiyama F, Nawa Y, Shimada S, Ohta N, Nakamura-Uchiyama F, Nawa Y, Shimada S, Ohta N: "Strongyloides venezuelensis : Mucosal sulfated carbohydrates determine the longitudinal distribution of adult worm in the host intestine"Exp Parasitol. 100. 179-185 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirayama K: "Generic factors associated with development of cerebral malaria and fibrotic schistosomiasis"Korean J Parasitol. 40. 165-172 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 太田伸生: "看護のための最新医学講座第4巻"中山書店. 3 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang R, Yashida A, Kumagai T, Kawaguchi H, Maruyama H, Suzuki T, Itoh M. El-Malky M, Ohta N.: "Vacctination with calpain induces a th1-biased protective immune response against Schistosoma japonicum"Infection and Immunity. 69. 386-391 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] He H, Zhang R, Kawaguchi H, Itoh M, Chen Y, Ohta N.: "Role of testosterone in host-parasite interaction during murine experimental infection of Schistosoma japonicum"Japanese Journal of Tropical Medicine. 29. 1-4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okumnura-Noji, K., Sasai, K., Zlian, R., Kawaguchi, H., Maruyama.H., Tada.T., Takaliashi, H., Okazaki, M., Miida.T., Sakuina, N., Kimura, G., Ohta, N., Yokoyama, S.: "Cholesteryl ester transfer protein deficiency causes slow egg embryonation of Schistosoma japonicum"Biochemical and Biophysical Research Communication. 286. 305-310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida A, Maruyama H, Kumagai T, Amano T, Kobayashi F, Kuribayashi K, Ohtaa N.: "Enhanced UV ♀1tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Thl-mediated response"Parasitology International. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] EI-Malky M, Maruyama H, Hirabayashi Y, Shimada S.Yoshida A, Amano T, Tominaga A, Takatsu K, Ohtaa N.: "Interleukin-5-dependent mechanisms enhance intestinal immunity against adult nematode Storongyloides venezuelensis"Parasite Immunology. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirayama K: "Immunogenetic Analysis of Severe Forms of Parasitic diseases"Acta Med. Nagasaki. 46. 1-5 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 太田伸夫: "看護のための最新医学講座第4巻 神経系の感染症"中山書店(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhang R,Takahashi S,Maruyama H,Yoshida A,Yabu Y,Shirai T & Ohta N.: "Cloning and molecular characterization of calpain, a calcium-activated neutral proteinase, from different strains of Schistosoma japonicum."Parasitology International. 48. 233-242 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshida A,Maruyama H,Amano T,Kobayashi F,Zhang R,Himeno K & Ohta N.: "Schistosoma mansoni infection cancels the susceptibility to Plasmodium chabaudi through induction of Th1-dominant circumstances in the susceptible A/J mice."International Immunology. 12. 1117-1125 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Maruyama H,Osada Y,Yoshida A,Futakuchi M,Kawaguchi H,Zhang R,Fu J,Shirai T & Ohta N.: "Protective mechanisms against the intestinal nematode, Strongyloides venezuelensis, in Schistosoma japonicum-infected mice."Parasite Immunology. 22. 279-286 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhang R,Yoshida A,Kumagai T,Kawaguchi H,Maruyama H,Suzuki T,Itoh M,El-Malky M & Ohta N.: "Vacctination with calpain induces a th1-biased protective immune response against Schistosoma japonicum."Infection and Immunity. 69. 386-391 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] He H,Zhang R,Kawaguchi H,Itoh M,Chen Y & Ohta N.: "Role of testosterone in host-parasite interaction during murine experimental infection of Schistosoma japonicum."Japanese Journal of Tropical Medicine. (in press)..

    • Related Report
      2000 Annual Research Report
  • [Publications] 太田伸生,吉田彩子: "寄生虫と生体防御"Biothrapy. 14. 597-602 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chen H,Nara T,Zeng X,Satoh M,Wu G,Kojima S,Zhang S & Hirayama K.: "Vaccination of domestic pig with recombinant paramyosin against Schistosoma japonicum in China."Vaccine. 20. 2142-2146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nara T,Hashimoto T & Aoki T: "Evolutionary implications of the mosaic pyrimidine-bosynthetic pathway in eukaryotes."Gene. 257. 209-222 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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