ABSTRACT
We generated highly chloroquine (CQ)-resistant (ResCQ) Plasmodium yoelii parasites by stepwise exposure to increasing concentrations of CQ and CQ-sensitive parasites (SenCQ) by parallel mock treatments. No mutations in genes that are associated with drug resistance were detected in ResCQ clones. Autophagy-related genes were highly upregulated in SenCQ compared to ResCQ parasites during CQ treatment. This indicates that CQ resistance can be developed in the malaria parasite by the inhibition of autophagy as an alternative drug resistance mechanism.
Subject(s)
Antimalarials , Chloroquine , Drug Resistance , Plasmodium yoelii , Protozoan Proteins , Humans , Antimalarials/pharmacology , Antimalarials/therapeutic use , Chloroquine/pharmacology , Chloroquine/therapeutic use , Drug Resistance/genetics , Malaria/drug therapy , Malaria/parasitology , Protozoan Proteins/genetics , Plasmodium yoelii/drug effects , Plasmodium yoelii/geneticsABSTRACT
Here, we present the construction of an attenuated herpes simplex virus type-1 (HSV-1)-vectored vaccine, expressing three liver-stage (LS) malaria parasite exported proteins (EXP1, UIS3 and TMP21) as fusion proteins with the VP26 viral capsid protein. Intramuscular and subcutaneous immunizations of mice with a pooled vaccine, composed of the three attenuated virus strains expressing each LS antigen, induced sterile protection against the intravenous challenge of Plasmodium yoelii 17X-NL salivary gland sporozoites. Our data suggest that this malaria vaccine may be effective in preventing malaria parasite infection using practical routes of immunization in humans.
