RNA-based
vaccine represents an irresistible and safe immunization strategy with decreasing theoretical risks of genomic integration and malignant cell transformation. To our knowledge, however, there is no report about development of
RNA vaccine against
Toxoplasma gondii infection. We have previously demonstrated that the recombinant T. gondii
nucleoside triphosphate hydrolase-II (
NTPase-II)
protein is able to provide protective Th1 cell-mediated immunity against T. gondii. Herein, we evaluated the immunogenic potential of a
self-amplifying RNA vaccine-encoding T. gondii
NTPase-II gene, RREP-
NTPase-II, delivered by a synthetic
lipid nanoparticle (LNP). Immunization of mice with naked RREP-
NTPase-II induced a strong cellular and humoral immune response with high-
IgG antibody titers and IFN-γ production. The immunized mice displayed significantly prolonged survival time and reduction in brain parasite load (46.4%) compared with control group. Furthermore, mice vaccinated with RREP-
NTPase-II-encapsulated LNP displayed significantly enhanced protection against acute
infection as well as
chronic infection with PRU
cyst, which shows 62.1% reduction in brain
cyst burden in comparison to control group. These results suggest that the combination of self-amplifying
RNA and LNP ion would be beneficial to the development of a safe and long-acting
vaccine against
toxoplasmosis.