A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum

摘要: Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current vitro pre-erythrocytic (PE) models for Plasmodium vivax P. falciparum lack the efficiency necessary rapid identification effective evaluation of new vaccines drugs, especially targeting late liver-stage development hypnozoites. Herein we report 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes. Hepatocyte physiology is maintained at least 30 days supports hypnozoites complete maturation schizonts. Our multimodal analysis antimalarial research identifies important PE inhibition mechanisms: immune antibodies against sporozoite surface proteins functionally inhibit stage ion homeostasis essential schizont hypnozoite viability. This model can be implemented laboratories disease-endemic areas to accelerate vaccine drug discovery research.