A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum
書誌事項
- 公開日
- 2018-05-09
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-018-04221-9
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models for<jats:italic>Plasmodium vivax</jats:italic>and<jats:italic>P</jats:italic>.<jats:italic>falciparum</jats:italic>lack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes. Hepatocyte physiology is maintained for at least 30 days and supports development of<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>hypnozoites and complete maturation of<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>and<jats:italic>P</jats:italic>.<jats:italic>falciparum</jats:italic>schizonts. Our multimodal analysis in antimalarial therapeutic research identifies important PE inhibition mechanisms: immune antibodies against sporozoite surface proteins functionally inhibit liver stage development and ion homeostasis is essential for schizont and hypnozoite viability. This model can be implemented in laboratories in disease-endemic areas to accelerate vaccine and drug discovery research.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 9 (1), 1837-, 2018-05-09
Springer Science and Business Media LLC
