Malaria remains a life-threatening disease of public health concern and is the leading cause of morbidity and mortality in children <5 years in Sub-Saharan Africa. The limited protective efficacy of the pre-erythrocytic sub-unit malaria vaccine, Mosquirix™, and blood-stage sub-unit vaccine candidates tested in the field has increased interest in pursuing alternative vaccine strategies such as the whole parasite vaccine approach. We are exploring the application of liposomes for the development of a whole parasite blood-stage malaria vaccine. This entails formulating killed, whole asexual blood-stage Plasmodium parasites with cationic adjuvant formulation 01 (CAF01). We hypothesise that this vaccine is capable of inducing strain and species-transcending protective immunity when evaluated in pre-clinical rodent models.
Our data demonstrate that a vaccine containing 107Plasmodium yoelii 17X parasitized red blood cells is highly immunogenic and provides good protective efficacy against homologous challenge in inbred and genetically outbred mice. Immunisation resulted in the induction of parasite-specific IgG and IgG1 responses, splenocyte proliferative responses, and a mixed Th1/Th2/Th17 cytokine response. The addition of synthetic Monophosphoryl Lipid A (PHAD®) to the vaccine formulation did not improve this vaccine’s efficacy. A Plasmodium chabaudi CAF01 vaccine provides good protective efficacy against homologous challenge in female C57BL/6 mouse strain.
Mechanistic studies demonstrated that CD4+ T cells and B cells play a critical role in protective immunity. Following the passive transfer of immune serum, mice were not protected from challenge indicating that antibodies do not appear to contribute to protection. Pro-inflammatory Th1-type cytokines IFN-γ and TNF-α also played a role in controlling parasitemia and survival. Depletion of macrophages did not impact on vaccine efficacy. Future studies will (i) assess heterologous protective efficacy and (ii) further examine the role of different immune compartments in protection. Overall, these results will inform the transition of this vaccine candidate into clinical trials.