Immune Response Modifying Effects of Bee Venom Protein [Melittin]/Autoclaved L. donovani complex in CD1 Mice: The Search for New Vaccine Adjuvants

Abstract

Visceral leishmaniasis (VL) is a major cause of morbidity/mortality in remote areas of East Africa. Vaccines for VL can provide an effective control measure to help control/eliminate this fatal disease. To date there is no effective anti-leishmanial vaccine. There is an urgent need to develop effective adjuvants-potentiated anti-leishmanial vaccines. Bee venom protein, melittin is a natural substance that is reported to boost the immune system providing rapid non–specific defense against infections. This study aimed to determine the immune response modifying effects of melittin and melittin/Autoclaved Leishmania donovani [ALD] complex on Swiss CD1 Albino mice. One hundred and eighty five CD1 mice were divided into control [no vaccine] and vaccine groups [3 doses of ALD alone, melittin, melittin/ALD mixture or melittin-adsorbed ALD]. Whole blood cytokines levels [IL-10, IFN-γ and TNF-α] were measured using commercial ELISA kits. ALD alone group showed significant increase in mean levels of IL-10, IFN-γ and TNF-α compared to controls [p=0.00004, p=0.01 and p=0.00001 respectively]. The Melittin and Melittin/ALD mixture-vaccinated mice showed significant increase in IL-10 and IFN-γ mean levels [IL-10 p=0.00001, p=0.00003; IFN-γ p=0.03, p=0.035 respectively], while the mean levels of TNF-α decreased significantly [p=0.00009, p=0.001] compared to controls. Melittin-adsorbed ALD reduced significantly the mean levels of IL-10, IFN-γ and TNF-α [p=0.00001, p=0.00008 and p=0.000001 respectively]. In conclusion, melittin alone and Melittin/ALD complex affected significantly Th1 and Th2 immune responses in Swiss CD1 Albino mice. Meltttin could be a potentially effective adjuvant for future anti-leishmania vaccines.