Type II uracil auxotrophs elicit protective immunity to type I and type II T. gondii infection. Groups of C57BL/6 mice (n = 8) were vaccinated with the type II Pru Δku80 Δompdc::HXGPRT mutant, or groups of mice were left unvaccinated (naive). Mice were challenged with type I (RH) or type II (Pru Δku80::HXGPRT) infections 30 days after vaccination, and survival was monitored for 30 days. (A) Pru Δku80 Δompdc::HXGPRT mutant-vaccinated mice (○) or unvaccinated naive mice (▼) were challenged i.p. with 1000 tachyzoites of the virulent type I RH strain. (B) Pru Δku80 Δompdc::HXGPRT mutant-vaccinated mice (○) or unvaccinated naive mice were challenged intraperitoneally with 200 (▲) or 2 × 107 (▼) tachyzoites of the type II Pru Δku80::HXGPRT strain. (C) Naive or vaccinated mice (n = 4), as indicated, were treated with anti-CD8 antibody or isotype control antibody at the time of challenge infection with 4 × 107 type II Pru Δku80::HXGPRT tachyzoites. (D) Cyst burdens present in the brains of Pru Δku80 Δompdc::HXGPRT mutant-vaccinated mice that were rechallenged with 2 × 107 tachyzoites of the Pru Δku80::HXGPRT strain (n = 8) or present in naive mice that were challenged with 200 tachyzoites of the Pru Δku80::HXGPRT strain (n = 7). Cyst measurements were performed 31 days postinfection. **, P < 0.01; ****, P < 0.0001.