Malaria is the leading cause of illness and deaths among children <5 years in Sub-Saharan Africa. The limited protective efficacy of the Mosquirix™ malaria vaccine and blood-stage subunit vaccine candidates tested in the field kindled an interest in exploring alternative vaccine strategies such as the whole parasite approach and alternative delivery systems (i.e., use of strong adjuvant platforms) that would counteract challenges facing subunit vaccine development technology (i.e. antigen polymorphism, sub-optimal immunogenicity and waning efficacy). To further develop a whole parasite blood-stage malaria vaccine, this thesis extensively explored the application of cationic liposomes in a rodent malaria model. The vaccine consists of killed, whole asexual blood-stage Plasmodium parasites formulated with liposomal cationic adjuvant formulation 01, CAF01. CAF01 is a potent adjuvant system that has been proven safe for clinical use in humans and has been shown to elicit strong cellular immune responses in a tuberculosis disease model. In the context of a whole parasite blood-stage malaria vaccine development, this thesis focused on the development and pre-clinical evaluation of a CAF01-adjuvanted vaccine in rodent model(s) of malaria. Herein, the key three research aims explored include: optimization and pre-clinical evaluation of a killed, whole blood-stage CAF01 vaccine in rodent models; evaluation of the mechanisms of vaccine-mediated protection induced by a whole blood-stage CAF01 vaccine; and tracking of red blood cells (i.e., normocytes and reticulocytes) using biotinylation methodology to assess haemoglobin dynamics and differential clearance of parasitized red blood cells to provide further insight on how the protective immune responses induced by Plasmodium yoelii 17X (Py17X) CAF01 are working in vaccinated mice. [...]