Determination of the adjuvant potential of bacille calmette guérin with culture derived leishmania major soluble exo-antigens

Abstract

Leishmaniasis is one of the neglected diseases that afflicts residents of developing countries. To date, there are no proven vaccines against this disease. Previous studies have shown that Leishmania major soluble exo-antigens (LmSEAgs) alone have the potential to confer protection to mice infected with L. major. There was need to investigate whether adjuvants could enhance the protective effects of the LmSEAgs the subject of this thesis. In this study, the immunoprophylatic and immunotherapeutic potential of Bacille Calmette Guérin (BCG) as an adjuvant was investigated. For immunoprophylaxis, susceptible BALB/c mice were vaccinated with LmSEAgs with or without BCG on day 0 and boosted on day 13, then challenged with L. major metacyclic promastigotes a week later. The control group was unvaccinated. While for immunotherapy, mice were vaccinated with LmSEAgs with or without BCG at day 21 and boosted on day 35. Disease progression was determined by measuring the size of lesions and quantifying parasite burdens in L. major infected footpads using a limiting dilution assay. While cytokine production from splenocytes was determined by flow cytometry. For both immunoprophylaxis and immunotherapy, mice produced significantly high levels of IFN-γ (P< 0.05) and low levels of interleukin IL-4, (P< 0.05) compared to the unvaccinated mice. This was corroborated with reduction in lesion sizes and parasite burden compared to the controls (P< 0.05). In comparison to the group of mice treated with LmSEAgs alone or BCG alone there was no significant difference in the levels of IFN-γ produced, lesion size reduction or parasite burdens (P>0.05) in both immunoprophylaxis and immunotherapy. In conclusion, the results show that BCG does not enhance the protective effect of LmSEAgs. Further studies should be done to search for molecules with potential of enhancing the immunotherapeutic and immunoprophylactic effects of LmSEAgs.