2016 Fiscal Year Research-status Report
Stimulating the host innate immune response to fight the early stages of malaria infection
| Project/Area Number |
16K21233
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| Research Institution | Nagasaki University |
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Principal Investigator |
カレトン リチャード 長崎大学, 熱帯医学研究所, 准教授 (10503782)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | Malaria / Pam2Cys / vaccine / antimalarial drug |
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| Outline of Annual Research Achievements |
During the last year we have tested the capacity of Pam2Cys to act against a variety of stages of the malaria parasite we have found that
1) Pam2Cys is able to consistently and dramatically reduce the numbers of malaria parasites able to survive in the liver of mice following a sporozoite inoculation. This reduction occurs both when Pam2Cys is administered prior to sporozoite inoculation, and 24 hrs following inoculation, proving that it is both preventative and curative of parasites at this stage
2) Pam2Cys does not have anti-schizontal effects against parasites in the blood, nor does it protect against a murine model of cerebral malaria
3) Pam2Cys does not protect against trypanosomes in the blood
4) Pam2Cys reduces the numbers of gametocytes that are infectious to mosquitoes, resulting in a reduction in transmission potential
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We have been successful in testing Pam2Cys as an anti-liver stage, anti-schizontal and anti-gametocyte drug. We have shown that whilst it is effective against gametocytes and liver stage parasites it is not active against blood stage parasites, and neither does it protect against experimental cerebral malaria. We are now moving on to attempts to characterise how Pam2Cys works against gametocytes and liver stage parasites.
This work would proceed faster if we had more people dedicated to working on it. At the moment, we only have myself and a PhD student, who is also concerned with other projects.
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| Strategy for Future Research Activity |
We will now focus on the following areas:
1) Elucidation of the mechanism of protection against liver stage parasites by analysing changes in the immune micro-environment of liver following Pam2Cys inoculation
2) We will test the ability of Pam2Cys to work in conjunction with antimalarial drugs to clear drug resistant malaria parasites from both the liver and the blood
3) We will determine how the parasite responds to Pam2Cys-mediated immune stress through transcriptome analysis of parasites that survive in the liver following Pam2Cys treatment
4)We will attempt to use Pam2Cys as an adjuvant along with single epitope vaccines of polymorphic antigens, in order to boost their capacity to protect against heterologous parasites.
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[Journal Article] Emergence of Indigenous Artemisinin Resistant Plasmodium falciparum in Africa2017
Author(s)
Lu F, Culleton R, Zhang M, Ramaprasad A, von Seidlein L, Zhou H, Zhu G, Tang J, Liu Y, Wang W, Cao Y, Xu S, Gu Y, Li J, Zhang C, Gao Q, Menard D, Pain A, Yang H, Zhang Q & Cao J.
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Journal Title
New England Journal of Medicine
Volume: 376
Pages: 991-993
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Genome-scale comparison of expanded gene families in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other Plasmodium species.2016
Author(s)
Ansari HA, Templeton JT, Subudhi AK, Ramaprasad A, Tang J, Lu J, Naeem R, Oguike MC, Benavente ED, Clark TG, Sutherland CJ, Barnwell JW, Culleton R＊, Cao J＊ and Pain A＊
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Journal Title
International Journal for Parasitology
Volume: 7519
Pages: 30135-30137
DOI
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies2016
Author(s)
Mita T, Culleton R, Takahashi N, M Nakamura, Tsukahara T, Hunja CW, Win ZZ, Htike WW, Marma AS, Dysoley L, Ndounga M, Dzodzomenyo M, Akhwale WS, Kobayashi J, Uemura H, Kaneko A, Hombhanje F, Ferreira MU, Bjorkman A, Endo H, Ohashi J
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Journal Title
Antimicrobial Agents and Chemotherapy
Volume: 60
Pages: 3340-3347
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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