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Infection and Immunity, September 1998, p. 4382-4388, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Partially Protective Vaccination Permits the Development of Latency in a Normally Virulent Strain of Toxoplasma gondii

George S. Yap,1,* Tanya Scharton-Kersten,1 David J. P. Ferguson,2 Dan Howe,3 Yasuhiro Suzuki,4,5 and Alan Sher1

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland1; Electron Microscopy Unit, Nuffield Department of Pathology, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom2; Department of Molecular Microbiology, Washington University, St. Louis, Missouri3; and Research Institute, Palo Alto Medical Foundation, Palo Alto,4 and Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford,5 California

Received 5 March 1998/Returned for modification 20 April 1998/Accepted 29 June 1998

The virulent RH strain of Toxoplasma gondii is acutely lethal in mice and fails to establish chronic infection. Vaccination of BALB/c mice with a soluble tachyzoite antigen preparation, STAg, in combination with the immunostimulatory cytokine interleukin-12 results in partial protection against RH lethal challenge. Nevertheless, brain tissue obtained from surviving, vaccinated mice as late as 1 year after RH infection contained latent parasite forms as demonstrated by subinoculation into naive recipients. The tachyzoites arising in the subinoculated animals were genetically indistinguishable from the original RH inoculum. Microscopic examination revealed that the persistent parasite forms present in the brains of vaccinated and challenged mice have a tissue cyst-like morphology and express the bradyzoite antigen BAG-1 but not the tachyzoite-specific antigen SAG-2 but are different from the cysts formed by avirulent T. gondii strains in that the internal parasite stages display ultrastructural features intermediate between tachyzoites and bradyzoites. Moreover, the zoites within the RH tissue cysts are clearly distinct from conventional bradyzoites in their sensitivity to pepsin-HCl digestion. In contrast to the observations made with partially resistant STAg/interleukin-12-vaccinated animals, no latent forms could be detected in brain tissue after RH challenge of mice immunized with a live attenuated tachyzoite vaccine which confers total protection against this parasite isolate. The above findings demonstrate the potential of a virulent T. gondii strain to generate latent parasite stages, a process which may be promoted under conditions of incomplete vaccination.

* Corresponding author. Mailing address: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 496-4881. Fax: (301) 402-0890. E-mail: gyap{at}atlas.niaid.nih.gov.

Infection and Immunity, September 1998, p. 4382-4388, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.