Malaria is a leading cause of morbidity and mortality. The possibility of a malaria vaccine was first realized in the 1940s, however a vaccine capable of inducing long-lasting protective immunity remains elusive. We have shown that a chemically attenuated whole parasite blood-stage vaccine offers profound protection in rodent models. Furthermore, a chemically attenuated P. falciparum whole parasite blood-stage vaccine was safe and immunogenic in malaria-naïve human volunteers. Although chemically attenuated malaria parasites are promising as a vaccine candidate, their application in malaria-endemic areas is logistically and practically challenging due to the requirement for the vaccine to contain a precise dose of intact parasitised red blood cells (pRBCs). Additionally, the inclusion of RBCs in the final product presents a small risk for the development of antibodies against RBC antigens. Thus, the development of a whole blood-stage parasite vaccine formulation with an alternative targeting/delivery system that does not rely on intact pRBCs for protective efficacy and prevents the induction of antibodies against RBC antigens is desirable. To address this we have developed a novel whole blood-stage parasite adjuvanted malaria vaccine. A liposomal vaccine formulation containing 107P. yoelii pRBC, synthetic monophosphoryl A and mannose provided robust protection against both homologous and heterologous blood-stage parasite challenge. CD4+ T cells and IFN-γ were critical mediators of the vaccine-induced protective immune response. Parasite-specific IgG, splenocyte proliferative responses and a mixed Th1/Th2/Th17 cytokine response were induced following vaccination. Lyophilisation of this formulation did not result in loss of potency, demonstrating compatibility with deployment into the field. In preparation for transitioning this vaccine candidate into clinical evaluation, further experiments were undertaken with a formulation containing 107P. falciparum pRBC, and it was shown to be similarly immunogenic in mice. These data support transitioning this novel whole blood-stage parasite malaria vaccine formulation into clinical studies.