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Infection and Immunity, December 2009, p. 5380-5388, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00649-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain{triangledown}

Jason P. Gigley,{dagger} Barbara A. Fox, and David J. Bzik*

Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, New Hampshire 03756

Received 8 June 2009/ Returned for modification 7 July 2009/ Accepted 15 September 2009

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 cps1-1 vaccine strain 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 naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-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 the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain 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 nonreplicating type I uracil auxotroph cps1-1 strain.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Dartmouth Medical School, Rm. 652E, Borwell Building, 1 Medical Center Drive, Lebanon, NH 03756. Phone: (603) 650-7951. Fax: (603) 650-6223. E-mail: david.j.bzik{at}dartmouth.edu

{triangledown} Published ahead of print on 21 September 2009.

Editor: W. A. Petri, Jr.

{dagger} Present address: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Ross Hall, 2300 I Street, Washington, DC 20037.

Infection and Immunity, December 2009, p. 5380-5388, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00649-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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