Application of adult worm and lung-stage antigens to immunize against schistosoma mansoni using cytokines as adjuvants

Different Schistosoma mansoni antigens; adult worm antigen [SWAP] and lung-stage antigen [SLAP] together with different cytokine adjuvants [Interferon-gamma and Interleukin-4] were used to immunize mice against. S. mansoni. Immunization program was directed towards the production of an intense immune response together with balanced T-helper1 and T-helper2 immune responses. The goal of immunization was not only to protect from infection but also to modulate the pathology inflicted by the parasite. Parameters like adult load, egg counts, anti-Schistosoma antibody titers and liver pathology were used to evaluate the different immunization scheme. SLAP antigen has proven to be a better antigen not only in protection but also in pathology modulation. SLAP plus IFN-gamma as an adjuvant was the best immunization regimen with almost 50% protection and a remarkable resolving of parasite pathology. Unexpectedly, IL- 4 had a weak but observed adjuvant protective effect. The results is a step in the path for a Schistosoma vaccine that guides the immune system towards a balanced response targeting the pathology induced by the parasite rather than the parasite itself

Heterologous antigens of toxoplasma gondii and salmonella typhimurium as adjuvants in an immunization program against schistosoma mansoni

Different bacterial and parasitic heterologous antigens were evaluated as adjuvants in a cocktail vaccine against Schistosoma mansoni. Killed Salmonella typhimurium and Toxoplasma gondii soluble antigens were used [each or both] combined with S. mansoni adult worm antigen [SWAP] to immunize against S. mansoni in murine models. Adult worm load, egg counts, anti-Schistosoma antibody titers and liver histopathology were used as measured parameters to evaluate the different study groups. Each of the used heterologous antigens has proven to be a beneficial adjuvant effect not only in protection but also in pathology modulation. Killed S. typhimurium was more efficient than T gondii soluble antigens. The most remarkable protective and pathology modulating effect was observed in the study group where both antigens were combined with SWAP in an immunization scheme indicating an additive response. Thus, the results of the current study proves that heterologous bacterial or parasitic antigens could be beneficial adjuvants helping to direct the immune response, to another parasite, towards a direction that confers both protection and pathology modulating effect

New effective and safe combination therapy for acute and chronic toxoplasmosis in murine models

Toxoplasma gondii is a protozoan parasite that infects humans and most species of warm blood animals. The most effective treatment for toxoplasmosis is the classic combination of pyrimethamine/sulfadiazine while the safest drug is spiramycin. These traditional anti-Toxoplasma drugs are either ineffective or have serious side effects that sometimes needs discontinuation of treatment. Both mouse [acute] and rat [chronic] models were used to evaluate a novel dipyridamole/allopurinol anti-Toxoplasma combination therapy that targets the purine salvage pathways of the parasite. The efficacy and safety of the new drugs were evaluated in comparison with traditional therapies; pyrimethamine/sulfadiazine and spiramycin. The life expectancy of mice in dipyridamole/ allopurinol group was significantly increased in comparison to other drug groups and almost doubled in relation to the infection control group. A significant reduction of anti-Toxoplasma antibody titers was only present in dipyridamole/allopurinol group in comparison to the infection control groups in both acute and chronic states of infection. The drug proves to be safe as evidenced by normal blood parameters reflecting no sign of drug toxicity. Pyrimethamine/sulfadiazine combination was second in efficacy while spiramycin was second in safety

Potential role of rolipram, a specific phosphodiestrase inhibitor, in preventing the establishment of a chronic state of toxoplasma gondii infection

Progression to a chronic state of the disease after an initial, mostly asymptomatic, acute phase is the normal fate of Toxoplasma gondii infection in immunocompetent hosts. Parasite reactivation of established chronic stage has serious manifestations on immunocompromised hosts. Tumor necrosis factor [TNF]- alpha, Interleukin [IL]-12 and cAMP have pivotal roles in tachyzoite to bradyzoite conversion and establishment of a chronic state of the disease. Rolipram, a specific phosphodiestrase inhibitor, has different regulatory roles on these factors. A daily oral dose of 10 mg/kg of rolipram was given to a group of mice, one week after T. gondii infection and for three weeks. Rolipram was found to have a great impact in preventing progression of chronic state and in mitigation of the pathology of this stage. Toxoplasma gondii tissue cyst load in mice brains has showed almost 4-fold reduction with the use of rolipram. The drug also mitigated the inflammation and pathologic processes in liver and more evident in the brain. Anti-Toxoplasma antibody titers are also significantly reduced in rolipram-treated group

Evaluation of the inhibtory effects of dipyridamole analogous on growth and multiplication of toxplasma gondii in culture

A new array of therapeutic agents [dipyridamole and four of its analogues], interfering with adenosine transport through the parasite plasma membrane, was evaluated for the first time in this study as potential drugs for T. gondii. A concentration of 10 uM of each drug was used in a triplicate of monolayers of cultured human foreskin fibroblasts [HFF] infected with tachyzoites of the RH strain of T. gondii. Different parameters of parasite growth and multiplication were scored 24 hours later. The dipyridamole analogues RE498 and BIBW22 along with dipyridamole itself showed a significant inhibitory effect, especially on the parasite ability to infect host cells and on the overall parasite multiplication. RE541 showed moderate inhibitory effects, while the last analogue [RE57] had almost no effect on parasite growth. These results showed that dipyridamole and some of its analogues could represent effective and safe drugs for the treatment of toxoplasmosis, especially in immunocompromised patients and if combined with other drugs that could interfere with the alternative metabolic pathway of other purines

reciprocal heterologous protection between trichinella spiralis and toxoplasma gondil concurrently present in experimental murine models

In this study, a different view of polyparasitism was demonstrated. The influence of the immunological environments created by two biologically different parasites on the pathogenesis of each other was evaluated. Swiss albino mice were sequentially infected with the intracellular protozoan Toxoplasma gondii [acute and latent] which elicits a T-Helper 1 [Th1]- polarized immune response and the helminth parasite Trichinella spiralis whose infection is predominated by a Th2 response. The results showed a significant heterologous protection from one parasite towards the other. There was a highly significant lower Trichinella muscle larvae burden in mixed infection group compared to single Trichinella infection in spite of delayed intestinal adult worm expulsion in the mixed infection group. A highly significant lower burden of T. gondii brain cysts in mixed infection compared to single latent Toxoplasma infection was also demonstrated. Concerning the anti-Toxoplasma antibody response, there was a significant lower level in the latent Toxo-Trich. group compared to the group of latent toxoplasmosis only