Abstract
Despite several decades of extensive research, the development of a highly efficacious malaria vaccine has yet to be accomplished. While the RTS,S malaria vaccine candidate shows the potential to prevent a substantial number of clinical malaria cases, significant improvements in protective efficacy are still needed. Multiple studies have shown that RTS,S induces protective antibody and CD4+ T-cell responses, but limited or negligible CD8+ T cells. In this study, we evaluated the immunogenicity and protective capacity of full-length recombinant P. falciparum circumsporozoite protein (CSP) administered with the novel cationic liposomal adjuvant system CAF09. Using newly developed transgenic rodent malaria parasites expressing the full-length P. falciparum CSP, we demonstrate that this liposome-based protein-in-adjuvant formulation is capable of inducing robust antibody and CD8+ T-cell responses that strongly inhibit parasite infection and development of liver stages, conferring durable sterilizing immunity. These findings underscore the potential of liposome-based adjuvants for inducing robust humoral and CD8+ T-cell responses and warrant further studies toward the development of novel subunit vaccine formulations with this adjuvant system.