1921
Volume 95, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

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 GAP-lacking expression of multidrug resistance-associated protein (MRP2) (PbΔ) 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 PbΔ sporozoites. Low-dose immunization using 400 PbΔ 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 PbΔ-challenged C57BL/6J mice were reduced by 86% ± 5% on average compared with naive control mice. The mid-to-late arresting PbΔ GAP was equipotent in induction of protective immunity to the early arresting PbΔΔ GAP. The combined data support a clear basis for further exploration of parasites lacking as a suitable GAP vaccine candidate.

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2016-08-03
2020-10-27
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Supplementary PDF

  • Received : 21 Mar 2016
  • Accepted : 04 May 2016
  • Published online : 03 Aug 2016
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