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  • Title: Protective Efficacy Induced by Genetically Attenuated Mid-to-Late Liver-Stage Arresting Plasmodium berghei Δmrp2 Parasites.
    Author: van der Velden M, Rijpma SR, Verweij V, van Gemert GJ, Chevalley-Maurel S, van de Vegte-Bolmer M, Franke-Fayard BM, Russel FG, Janse CJ, Sauerwein RW, Koenderink JB.
    Journal: Am J Trop Med Hyg; 2016 Aug 03; 95(2):378-82. PubMed ID: 27296385.
    Abstract:
    Whole parasite immunization strategies employing genetically attenuated parasites (GAP), which arrest during liver-stage development, have been applied successfully for induction of sterile malaria protection in rodents. Recently, we generated a Plasmodium berghei GAP-lacking expression of multidrug resistance-associated protein (MRP2) (PbΔmrp2) that was capable of partial schizogony in hepatocytes but showed complete growth arrest. Here, we investigated the protective efficacy after intravenous (IV) immunization of BALB/c and C57BL/6J mice with PbΔmrp2 sporozoites. Low-dose immunization using 400 PbΔmrp2 sporozoites induced 100% sterile protection in BALB/c mice after IV challenge with 10,000 wild-type sporozoites. In addition, almost full protection (90%) was obtained after three immunizations with 10,000 sporozoites in C57BL/6J mice. Parasite liver loads in nonprotected PbΔmrp2-challenged C57BL/6J mice were reduced by 86% ± 5% on average compared with naive control mice. The mid-to-late arresting PbΔmrp2 GAP was equipotent in induction of protective immunity to the early arresting PbΔb9Δslarp GAP. The combined data support a clear basis for further exploration of Plasmodium falciparum parasites lacking mrp2 as a suitable GAP vaccine candidate.
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