Protective Efficacy Induced by Genetically Attenuated Mid-to-Late Liver-Stage Arresting Plasmodium berghei Δmrp2 Parasites.

Autor:	van der Velden M; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands., Rijpma SR; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands., Verweij V; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands., van Gemert GJ; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Chevalley-Maurel S; Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., van de Vegte-Bolmer M; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Franke-Fayard BM; Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Russel FG; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands., Janse CJ; Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Sauerwein RW; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Koenderink JB; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands. jan.koenderink@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	The American journal of tropical medicine and hygiene [Am J Trop Med Hyg] 2016 Aug 03; Vol. 95 (2), pp. 378-82. Date of Electronic Publication: 2016 Jun 13.
DOI:	10.4269/ajtmh.16-0226
Abstrakt:	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. (© The American Society of Tropical Medicine and Hygiene.)
Databáze:	MEDLINE
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