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EPIDEMIOLOGICAL STUDY FOR DEVELOPING SERA MALARIA VACCINE

Research Project

Project/Area Number 11694278
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field 寄生虫学(含医用動物学)
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

HORII Toshihiro  OSAKA UNIVERSITY, RESEARCH INSTITUTE FOR MICROBIAL DISEASES, PROFESSOR, 微生物病研究所, 教授 (80142305)

Co-Investigator(Kenkyū-buntansha) NIWA Atsuko  KINKI UNIVERSITY, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (60122082)
MITAMURA Toshihide  OSAKA UNIVERSITY, RESEARCH INSTITUTE FOR MICROBIAL DISEASES, ASSISTANT PROFESSOR, 微生物病研究所, 講師 (80268846)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2000: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsPlasmodium falciparum / MALARIA VACCINE / SERA / SE47' PROTEIN / IgG3 / UGANDA / SEROEPIDEMIOLOGY / PARASITEMIA / SE47'タンパク質 / lgG3 / 抗体価 / マラリア原虫率 / 発熱
Research Abstract

P.falciparum serine rich antigen (SERA) is a promising malaria vaccine candidate antigen. SERA is a 126 kDa asexual blood stage antigen produced in large amounts specifically during late trophozoite and schizont stages. We have expressed N-terminal domain (SE47') and central domain (SE50A) of SERA protein in E.coli by synthesizing the genes with a changed codon usage suitable for expressing in E.coli. SE47'protein but not SE50A protein induced the parasite growth inhibitory antibodies in rat and mouse. In this project, we have examined the IgG subclass specific titers against SE47' and SE50A in residents of Atopi Parish, a region of intense malaria transmission in Northern Uganda, to see the natural immune responses against these recombinant molecules. It has been demonstrated that the IgG3 is the predominant response to SE47' in residents of Atopi Parish and that increased levels of IgG3 antibodies correlated with clinical immunity in children under 10 years old. Predominant response to SE50A was, however, IgG1 subclass and had no correlation with the clinical immunity. We have further found the following correlation ; 1) the increased levels of the IgG3 correlated with the lower parasite density in peripheral blood of the residents. 2) The growth inhibition of the cultured parasites by individual serum correlated with the levels of IgG3 antibodies against SE47' in the serum. 3) The observed parasite growth inhibition was neutralized by adding the recombinant SE47' protein.
In summary, we have concluded that the anti-SE47' IgG3 is the major anti-malaria immune response in human that has been long time unknown. The obtained information will accelerate the malaria vaccine development with the recombinant protein of the N-terminal domain of SERA.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Sakai T.,Horii T.,Hisaeda H.,Zhang M.,Ishii K.,Nakano Y.,Izumi K.,Nitta Y.,Miyazaki J.-I. & Himeno K.: "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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pang X.-L.Mitamura T.& Horii T.: "Antibodies specific to N-terminal domain of Plasmodium falciparum serine repeat antigen (SERA) agglutinate merozoites and schizonts."Infection and Immunity. 67. 1821-1827 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belperron,A.A.,Feltquate,D.,Fox,B.A.,Horii T.& 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Hanada,T.Mitamura,M.Fukasawa,P.A.Magistrado,T.Horii, & M.Nishijima: "Neutral sphingomyelinase activity dependent on Mg^<2+> and anionic phospholipids in the intraerythrocytic malaria parasite Plasmodium falciparum."Biochemical Journal. 346. 671-677 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitamura T.,Hanada K.,Ko-Mitamura EP.,Nishijima M.& Horii T.: "Serum factors governing intraerythrocytic development and cell cycle progression of Plasmodium falciparum."Parasitology International. 49. 219-229 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okech,B.A.,Nalunkuma,A.,Okello,D.,Pang,X,-L.,Suzue,K.,Li,J.,Horii,T.& Egwang,T.G.: "Natural human IgG subclass responses to Plasmodium falciparum serine repeat antigen (SERA) in Uganda."American Journal of Tropical Medicine and Hygiene. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Liu Q.,Ferreira M.U.,Ndawi B.T.,Ohmae H.,Adagu I.S.,Morikawa T.,Horii T.,Isomura S.& Kawamoto F.: "Sequence diversity of serine repeat antigen gene exon II of Plasmodium falciparum and in worldwide collected wild isolates."South East 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
      2000 Final Research Report Summary
  • [Publications] Sakai T., Horii T., Hisaeda H., Zhang M., Ishii K., Nakano Y., Izumi K., Nitta Y., Miyazaki J.-I.& Himeno K.: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pang X.-L.Mitamura T.& Horii T.: "Antibodies specific to N-terminal domain of Plasmodium falciparum serine repeat antigen (SERA) agglutinate merozoites and schizonts."Iimfection and Immunity. 67. 1821-1827 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Belperron, A.A., Feltquate, D., Fox, B.A., Horii T.& 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."Iimfection and Immunity. 67. 5163-5169 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Hanada, T.Mitamura, M.Fukasawa, P.A.Magistrado, T.Horii, & M.Nishijima: "Neutral sphingomyelinase activity dependent on Mg^<2+> and anionic phospholipids in the intraerythrocytic malaria parasite Plasmodium falciparum."Biochemical Journal. 346. 671-677 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitamura T., Hanada K., Ko-Mitamura EP., Nishijima M.& Horii T.: "Neutral sphingomyelinase activity dependent on Mg^<2+> and anionic phospholipids in the intraerythrocytic malaria parasite Plasmodium falciparum."Parasitology International. 49. 219-229 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okech, B.A., Nalunkuma, A., Okello, D., Pang, X.-L., Suzue, K., Li, J., Horii T.& Egwang, T.G.: "Natural human IgG subclass responses to Plasmodium falciparum serine repeat antigen (SERA) in Uganda."American Journal of Tropical medicine and Hygiene. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Liu Q., Ferreira M.U., Ndawi B.Y., Ohmae H., Adagu I.S., Morikawa T., Horii T., Isomura S.& Kawamoto F.: "Sequence diversity of serine repeat antigen gene exon II of Plasmodium falciparum and in worldwide collected wild isolates."South East 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
      2000 Final Research Report Summary
  • [Publications] K.Hanada,T.Mitamura,M.Fukasawa,P.A.Magistrado,T.Horii,& M.Nishijima: "Neutral sphingomyelinase activity dependent on Mg^<2+> and anionic phospholipids in the intraerythrocyic malaria parasite Plasmodium falciparum."Biochemical Journal. 346. 671-677 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mitamura T.,Hanada K.,Ko-Mitamura E.P.,Nishijima M.& Horii T.: "Serum factors governing intraerythrocytic development and cell cycle progression of Plasmodium falciparum."Parasitology International. 49. 219-229 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okech,B.A.,Nalunkuma,A.,Okello,D.,Pang,X-L.,Suzue,K.,Li,J.,Horii,T.& Egwang,T.G.: "Natural human IgG subclass responses to Plasmodium falciparum serine repeat antigen (SERA) in Uganda."Amerlcan Journal of Tropical Medicine and Hygiene. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Liu Q.,Ferreira M.U.,Ndawl B.T.,Ohmae H.,Adagu I.S.,Morikawa T.,Horli T.,Isomura S.& Kawamoto F.: "Sequence diversity of serine repeat antigen gene exon II of Plasmodium falciparum and in worldwide collected wild isolates."South East Asian Journal of Tropical Medicine and Hyglene. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 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)

    • Related Report
      1999 Annual Research Report
  • [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. 22. 1321-1327 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 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)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wang P.,Brogey P.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)

    • Related Report
      1999 Annual Research Report
  • [Publications] 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)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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