Protective effect of a DNA vaccine delivered in attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice

Abstract

Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The T. gondii surface antigen protein SAG1 is a significant candidate vaccine against toxoplasmosis. In this study, we evaluated safety, stability of ZJ111/pcDNA3-SAG1, a DNA vaccine delivered in attenuated Salmonella typhimurium, and immune responses induced by immunizing ICR mice orally with ZJ111/pcDNA3-SAG1 of different doses. Mice had no significant differences in body weight between the groups before immunization and at week 4 after the booster immunization. The ZJ111/pcDNA3-SAG1 was eventually eliminated from the spleen and liver on week 6 post-immunization. The plasmid pcDNA3-SAG1 was stably maintained over 90% of the attenuated S. typhimurium population after 100 generations of growth in antibiotic-free media. Oral immunization of mice with ZJ111/pcDNA3-SAG1 elicited specific humoral responses and stimulated proliferation of splenocytes ( P < 0.05). The cellular immune response was associated with the production of IFN-γ, indicating that a Th-1 type response was elicited, which was confirmed by the production of large amounts of IgG2a ( P < 0.01). Mice immunized with ZJ111/pcDNA3-SAG1 displayed significant protection against an intraperitoneally challenge with 500 tachyzoite forms of T. gondii RH strain. Vaccination at 10 7 and 10 8 CFU per mice provided a 20% and 10% survival rate comparing 100% mortality of the non-immunized mice, exhibiting longer living time and better survival rate. These results confirmed a DNA vaccine delivered in attenuated S. typhimurium, ZJ111/pcDNA3-SAG1, can elicit specific immune response as well as provide effective protection against T. gondii infection, and the dosage of 10 7 CFU was a most considerate one.