Mic1-3 Knockout of Toxoplasma Gondii is a Successful Vaccine Against Chronic and Congenital Toxoplasmosis in Mice

Background: We evaluated a new vaccine, Mic1-3KO, against both chronic and congenital toxoplasmosis in mice. Mic1-3KO is a mutant strain of Toxoplasma gondii RH that lacks the mic1 and mic3 genes.

Methods: OF1 mice were vaccinated with Mic1-3KO tachyzoites and challenged orally with T. gondii (strain 76K). Immune responses and protection against chronic infection (cyst load in brain tissue) and congenital infection (maternofetal transmission, survival, body weight, and chronic infection in pups) were evaluated.

Results: Mic1-3KO induced a strong humoral and cellular T helper (Th) 1 response and conferred highly significant protection against chronic infection (>96% reduction in cysts in brain tissue). Fewer infected fetuses were observed in vaccinated dams that were infected during pregnancy than in nonvaccinated infected dams (4.6% vs. 33.3%). All pups born to vaccinated infected dams survived and had the same weight as those born to nonvaccinated uninfected dams. Furthermore, they had significantly fewer cysts in brain tissue (>91%) than pups from nonvaccinated infected dams. During pregnancy, protection against congenital disease was associated with a cellular Th1 response regulated by interleukin-10. One month after delivery, vaccinated infected dams had >96% fewer cysts in their brain tissue than nonvaccinated infected dams.

Conclusion: Mic1-3KO is an effective vaccine against chronic and congenital toxoplasmosis.