Soluble <i>Leishmania</i> Antigens Plus Pristane Adjuvant Induce Partial Cross-protection Against Leishmaniasis in BALB/c mice

Leishmaniasis is a vector-borne parasitic disease of global concern. The disease is currently controlled by vector management and treatment of infected individuals as there is no approved vaccine. This study evaluated the safety, immunopotency and cross-immunity in BALB/c mice vaccinated with soluble Leishmania major or L. donovani antigens co-administered with 2,6,10,14-tetramethylpentadecane (pristane) and challenged with either L major or L.donovani virulent parasites. Safety was assessed by establishing dose-dependent blood-cell and platelet counts at 28 days post-injection, immunopotency was determined by measurement of interferon-gamma (IFN-ɣ) and interleukin 10 (IL-10) production, and disease progression by measurement either footpad lesion and parasite load in case of L.major challenge or spleen parasite loads for L.donovani challenge at 45 days post-infection. There was no significant effect by pristane on blood cell and platelet counts, indicating that at 20ug/mL, pristane was safe to use as an adjuvant in mice. Mice vaccinated with soluble L. donovani antigens plus pristane and challenged with L. major had smaller infected footpad lesions and lower parasite loads compared to BCG-vaccinated and unvaccinated mice. Similarly, mice vaccinated with soluble L. major antigens plus pristane and challenged with L. donovani had lower splenic parasite loads than unvaccinated mice. These corresponded with increased production of IFN-ɣ and suppressed production of IL-10 in each of the vaccinated groups, suggesting an up-regulated protective T helper 1 (Th1) response. The results indicated that vaccination of BALB/c mice with pristane adjuvant co-administered with soluble Leishmania antigens promotes Th1 response that confers partial cross-immunity against infection with heterologous Leishmania parasites. Further investigations on the safety of pristane in the longer term as well as other factors other than Th1 cytokines production up-regulation that may influence cross-protection in Leishmania infections need to be investigated