Histopathology of active toxoplasmosis of myocardium. Photo courtesy of EP Ewing Jr. and CDC |
Toxoplasma gondii is a ubiquitous obligate, intracellular parasitic protozoan known to cause toxoplasmosis in a number of warm-blooded animals, including humans. This protist is transmitted to humans through the consumption of undercooked meat from infected animals, the ingestion of food or water contaminated with oocytes from infected cat feces, or by transplacental transmission. In healthy individuals, toxoplasmosis is relatively asymptomatic and self-limiting. However, this illness can silently affect pregnant women and result in severe consequences for the fetus including neurological impairment, chorioretinitis, or death. T. gondii can also affect immune-compromised individuals, resulting in cerebral or extra-cerebral toxoplasmosis.
Currently, the CDC considers toxoplasmosis to be one of the leading causes of death attributed to foodborne illness. Moreover, T. gondii infection in domestic animals represents a significant economic and public health threat due to the potential for foodborne outbreaks. Unfortunately, treatment of toxoplasmosis is difficult due to both the severe side-effects of the drug as well as the potential for re-infection. Thus, the development of effective preventative treatments is of great importance.
In recent study, Wang et al. analyzed the protective efficacy of recombinant T. gondii protein disulfide isomerase (PDI) as a potential target for the development of a novel vaccine. This particular antigen was chosen as a candidate vaccine target as it is soluble, demonstrates conserved homology among the three distinct clonal lineages of T. gondii strains, and is highly expressed on the outer surface of T. gondii tachyzoites. In this study, BALB/c mice were intranasally immunized with varying concentrations of recombinant T. gondii PDI (rTgPDI), and the resulting immunological response was evaluated by lymphoproliferative assays and by cytokine and antibody measurements. In addition to this analysis, immunized mice were also challenged with tachyzoites from T. gondii strain RH. Following this challenge, the survival time of the mice was assessed and the number of brain and liver tachyzoites enumerated.
From these analyses, the group discovered that immunization with 30 µg of rTgPDI demonstrated higher levels of anti-PDI antibody production, a strong lymphoproliferative response, and high levels of cytokine production as compare to the other doses tested. Further, mice immunized with rTgPDI demonstrated enhanced survival times and reduced levels of tachyzoites as compared to control mice. Overall, the results from the study demonstrated that immunization with rTgPDI elicited a protective immune response against T. gondii tachyzoites, thus suggesting that this recombinant protein may be a promising candidate for the development of a vaccine to prevent toxoplasmosis.