Long-term immunity to lethal acute or chronic Type II Toxoplasmosis gondii infection

Infect Immun. 2009 Sep 21. [Epub ahead of print]

Long-term immunity to lethal acute or chronic Type II Toxoplasmosis gondii infection is effectively induced in genetically susceptible C57BL/6 mice by immunization with an attenuated Type I vaccine strain

Gigley JP, Fox BA, Bzik DJ.

Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756 USA.

C57BL/6 (B6) mice are genetically highly susceptible to chronic Type II Toxoplasma gondii infections that invariably cause lethal Toxoplasmic encephalitis. We examined the ability of an attenuated Type I vaccine strain to elicit long-term immunity to lethal acute or chronic Type II infections in susceptible B6 mice. Mice immunized with the Type I vaccine strain cps1-1 were not susceptible to a lethal (100 cyst) challenge with the Type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naïve mice, regardless of the route of challenge infection. Remarkably, cps1-1 immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to Type II challenge infections persisted for at least 10 months after vaccination. While cps1-1 elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 elicited CD8(+) immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. Additionally, we show that uracil starvation of strain cps1-1 induces early markers of bradyzoite differentiation. Collectively these results suggest that more effective immune control of chronic Type II infection in the genetically susceptible B6 background is established by vaccination with the non replicating Type I uracil auxotroph strain cps1-1.

PMID: 19797073 [PubMed - as supplied by publisher]