2010 Fiscal Year Final Research Report
Malaria genetic diversity as a basis for parasite growth and pathogenicity
| Project Area | Matrix of Infection Phenomena |
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| Project/Area Number |
18073013
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Kazuyuki 大阪大学, 微生物病研究所, 招へい教授 (40047410)
ISHII Ken 医薬基盤研究所, プロジェクトリーダー (00448086)
ARISUE Nobuko 大阪大学, 微生物病研究所, 助教 (00242339)
TOUGAN Takahiro 大阪大学, 微生物病研究所, 助教 (20379093)
TAI Kumiko 大阪大学, 微生物病研究所, 教務職員 (00187907)
HAYAKAWA Toshiyuki 京都大学, 霊長類研究所, 特任助教 (80418681)
YAGI Masanori 大阪大学, 微生物病研究所, 特任研究員 (60452463)
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| Project Period (FY) |
2006 – 2010
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| Keywords | マラリア / Plasmodium / 遺伝子多型 / 多重遺伝子群 / SE36マラリアワクチン |
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| Research Abstract |
The major purposes of this research is to reveal the molecular basis of genetic diversity (polymorphism and gene family) of P. falciparum in conjunction with analysis of diversity and function of SERA gene family to which a candidate vaccine antigen, PfSERA5, belongs to. These would be the basis of SE36 malaria vaccine development.
We sequenced mitochondrial genome of 23 plasmodium species and constructed a phylogenetic tree that predicted all extant species of malaria parasites expanded to the host range rapidly around 3,800-2,500 million years ago (Malaria Big Ban). The analysis of nucleotide diversity in P. falciparum parasites collected from nine countries worldwide revealed that Africa is highest among these regions, suggesting that P. falciparum has been globally spread along with human migration out of Africa about 60,000 years ago. These are our new proposals on malaria evolution. Phylogenetic analysis of SERA multi-gene family of 18 Plasmodium species revealed that a large number of duplication of SERA gene is characteristic in primate parasites. We have built a draft genome sequence of simian malaria parasite P. cynomolgi that is closely related to human parasite P. vivax. Unlike the other vaccine candidate genes, a genetic diversity of PfSERA5 was found to be similar to those of house keeping genes. This observation further encourages our clinical development of SE36 malaria vaccine. We conducted Phase Ib clinical trial of SE36 malaria vaccine in Uganda. The 1 year follow-up study of the trial showed about 60% of protective efficacy. Finally, we have constructed SE36 second-generation malaria vaccine that includes innate immunity adjuvant, CpG and proved its efficacy in animal model.
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