Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice

In this study, we generated a tkl1 deletion mutant in the Toxoplasma gondii type 1 RH (RH Delta tkl1) strain and tested the protective efficacies of vaccination using RH Delta tkl1 tachyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RH Delta tkl1 mounted a strong humoral and cellular response as shown by elevated levels of anti-T gondii- specific IgG, IL-2, IL-12, IFN-gamma, and IL-10. All RH Delta tl1-vaccinated mice survived a lethal challenge with 1 X 10(3) tachyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugnivad strain. All mock-vaccinated plus infected mice have died. Vaccination also protected against cyst- or oocyst-caused chronic infection, reduced vertical transmission caused by oocysts, increased litter size, and maintained body weight of pups born to dams challenged with 10 oocysts on day 5 of gestation. In contrast, all mock-vaccinated plus oocysts-infected dams had aborted, and no fetus has survived. Vaccinated dams remained healthy postinfection, and their brain cyst burden was significantly reduced compared with mock-vaccinated dams infected with oocysts. In vivo depletion of CD4(+) T cells, CD8(+) T cells, and B cells revealed that CD8(+) T cells are involved in the protection of mice against T. gondii infection. Additionally, adoptive transfer of CD8(+) T cells from RH Delta tkl1-vaccinated mice significantly enhanced the survival of naive mice infected with the pathogenic strain. Together, these data reaffirm the importance of CD8(+) T cell responses in future vaccine design for toxoplasmosis and present T. gondii tkl1 gene as a promising vaccine candidate.