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The Toll-Like Receptor 2 agonist PEG-Pam2Cys as an immunochemoprophylactic and immunochemotherapeutic against the liver and transmission stages of malaria parasites
http://hdl.handle.net/10069/39455
http://hdl.handle.net/10069/39455844aa026-72d4-4e52-aef4-dc2897d6e465
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ISYK1173_Ernest.pdf (1.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-09-25 | |||||
| タイトル | ||||||
| タイトル | The Toll-Like Receptor 2 agonist PEG-Pam2Cys as an immunochemoprophylactic and immunochemotherapeutic against the liver and transmission stages of malaria parasites | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Malaria | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Plasmodium | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Pam2Cys | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | TLR-2 | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
ERNEST, MEDARD
× ERNEST, MEDARD |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 116545 | |||||
| 姓名 | アーネスト, メダード | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Both vaccine and therapeutic approaches to malaria are based on conventional paradigms; whole organism or single antigen epitope-based vaccines administered with or without an adjuvant, and chemotherapeutics (anti-malaria drugs) that are toxic to the parasite. Two major problems that limit the effectiveness of these approaches are i) high levels of antigenic variation within parasite populations rendering vaccination efficacy against all variants difficult, and ii) the capacity of the parasite to quickly evolve resistance to drugs. We describe a new approach to both protection from and treatment of malaria parasites that involves the direct stimulation of the host innate immune response through the administration of a Toll-Like Receptor-2 (TLR2) agonist. The activity of PEG-Pam2Cys against the hepatocytic stages, erythrocytic stages and gametocytes of the rodent malaria parasite Plasmodium yoelii was investigated in laboratory mice. We show that administration of PEG-Pam2Cys, a soluble form of the TLR2 agonist S-[2,3-bis(palmitoyloxy)propyl] cysteine (Pam2Cys), significantly and dramatically reduces the numbers of malaria parasites that grow in the livers of mice following subsequent challenge with sporozoites. We also show that treatment can also clear parasites from the liver when administered subsequent to the establishment of infection. Finally, PEG-Pam2Cys can reduce the numbers of mosquitoes that are infected, and the intensity of their infection, following blood feeding on gametocytaemic mice. These results suggest that this compound could represent a novel liver stage anti-malarial that can be used both for the clearance of parasites following exposure and for the prevention of the establishment of infection. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1173号 学位授与年月日:令和元年9月20日 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Author: Medard Ernest, Carol Hunja, Yuka Arakura, Yohei Haraga, Hussein M. Abkallo, Weiguang Zeng, David C. Jackson, Brendon Chua, Richard Culleton | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: International Journal for Parasitology: Drugs and Drug Resistance, 8(3), pp.451-458; 2018 | |||||
| 書誌情報 |
International Journal for Parasitology: Drugs and Drug Resistance 巻 8, 号 3, p. 451-458, 発行日 2019-09-20 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 22113207 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.ijpddr.2018.10.006 | |||||
| 権利 | ||||||
| 権利情報 | c 2018 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| その他のタイトル | ||||||
| その他のタイトル | マラリア原虫の肝臓期と伝播期に対する Toll様受容体2のアゴニストPEG-Pam2Cysを用いた免疫化学予防と免疫化学療法 | |||||
| 出版者 | ||||||
| 出版者 | Elsevier Ltd. | |||||
| 関係URI | ||||||
| 識別子タイプ | HDL | |||||
| 関連識別子 | http://hdl.handle.net/10069/39454 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17301 | |||||
| 学位授与機関名 | Nagasaki University (長崎大学) | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-09-20 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲医歯薬第1173号 | |||||
| 学位の種類 | ||||||
| 値 | 課程博士 | |||||
| 引用 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Nagasaki University (長崎大学), 博士(医学) (2019-09-20) | |||||
