Project/Area Number |
11694278
|
Research Category |
Grant-in-Aid for Scientific Research (A).
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
寄生虫学(含医用動物学)
|
Research Institution | OSAKA 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)
|
Keywords | Plasmodium 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.
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