%0 Journal Article
%T Protective Efficacy Induced by Genetically Attenuated Mid-to-Late Liver-Stage Arresting Plasmodium berghei ¦¤mrp2 Parasites
%A Blandine M. Franke-Fayard
%A Frans G. M. Russel
%A Geert-Jan van Gemert
%A Jan B. Koenderink
%A Maarten van der Velden
%A Marga van de Vegte-Bolmer
%A Robert W. Sauerwein
%A Sanna R. Rijpma
%A S¨¦verine Chevalley-Maurel
%A Vivienne Verweij
%J Archive of "The American Journal of Tropical Medicine and Hygiene".
%D 2016
%R 10.4269/ajtmh.16-0226
%X 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) (Pb¦¤mrp2) 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 Pb¦¤mrp2 sporozoites. Low-dose immunization using 400 Pb¦¤mrp2 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 Pb¦¤mrp2-challenged C57BL/6J mice were reduced by 86% ¡À 5% on average compared with naive control mice. The mid-to-late arresting Pb¦¤mrp2 GAP was equipotent in induction of protective immunity to the early arresting Pb¦¤b9¦¤slarp GAP. The combined data support a clear basis for further exploration of Plasmodium falciparum parasites lacking mrp2 as a suitable GAP vaccine candidate
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973185/