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

In this study, we generated a kl1 deletion mutant in the Toxoplasma gondii ype 1 RH (RHΔ kl1 ) strain and tested the protective efficacies of vaccination using RHΔ kl1 achyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RHΔ kl1 mounted a strong humoral and cellular response as shown by elevated levels of anti- T. gondii -specific IgG, IL-2, IL-12, IFN-γ, and IL-10. All RHΔ kl1 -vaccinated mice survived a lethal challenge with 1 × 10 3 achyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugniuad 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 agains T. gondii infection. Additionally, adoptive transfer of CD8 + T cells from RHΔ kl1 -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 presen T. gondii tkl1 gene as a promising vaccine candidate.