ABSTRACT
Background: Cationic immune stimulating complexes [PLUSCOMs] are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes [ISCOMs] derivatives and are able to elicit in vivo T cell responses against an antigen
Objective: To evaluate the effects of PLUSCOMs containing Leishmania major antigens [SLA] on the type of immune response generated in the murine model of leishmaniasis
Methods: PLUSCOMs consisting of 1, 2-dioleoyl-3-trimethylammonium-propane [DOTAP] were used as antigen delivery system/immunoadjuvants for soluble SLA. BALB/c mice were immunized subcutaneously, three times in 2-week intervals. Footpads swellings at the site of challenge and parasite loads were assessed as a measure of protection. The immune responses were also evaluated by determination of IgG subclasses and the level of IFN- gamma and IL-4 in cultured splenocytes
Results: There was no significant difference [p<0.05] between the sizes of lesions in mice immunized with different formulations. Also, there was no significant difference in the number of parasites in the footpad or spleen of all groups compared with the control group. The highest level of IFN- gamma secretion was observed in the splenocytes of mice immunized with PLUSCOM/SLA [p<0.001] and lower amounts of IL-4 was observed in PLUSCOM group [p<0.001] as compared to negative control
Conclusion: Our results indicated that SLA in different formulations generated an immune response with mixed Th1/Th2 response that was not protective enough despite the activation of CD4+ T cells with secreting IFN- gamma in groups which received PLUSCOM with antigen
ABSTRACT
An inoculation of virulent Leishmania major is known as leishmanization [LZ] which is proven to be the most effective control measure against Cutaneous Leishmaniasis [CL]. However, using LZ is restricted due to various side effects such as uncontrolled lesion development. In the present research, the efficacy of cationic nanoliposomes containing CpG oligodeoxynucleotides [CpG ODN] as an improved adjuvant delivery system was studied to diminish the lesion development and infection course of L. major after inoculation into the mice. BALB/c mice were inoculated subcutaneously [SC] with L. major plus empty DSPC, DSPC [CpG ODN], DSPC [Non CpG ODN], empty DMPC, DMPC [CpG ODN], DMPC [Non CpG ODN] or HEPES buffer. The results showed that group of mice received DMPC [CpG ODN] nanoliposomes developed a significantly smaller lesion and showed minimum number of L. major in the spleen and draining lymph nodes. In addition, using DMPC [CpG ODN] liposomes resulted in a Th1 type of immune response with a preponderance of IgG2a isotype which is concurrent with the production of DMPC [CpG] induced IFN-gamma in the spleen of the mice. Taken together, the results suggested that immune modulation using DMPC [CpG ODN] nanoliposomes might be a practical approach to improve the safety of LZ