Evaluation Of The Adjuvanticity Of Artemisinin With Soluble Leishmania Major Antigens In Balb/C Mice

ABSTRACT

Leishmania major is an obligate intracellular protozoan parasite that causes chronic cutaneous lesions that often result in disfiguring scars. Artemisinin, a well known antimalarial drug, has been shown to be efficacious against Leishmania parasites both in vivo and in vitro. This study sought to determine the adjuvant potential of artemisinin when administered with a soluble leishmanial antigen. To test this hypothesis, seventy-two female BALB/c mice were randomly assigned into six treatment groups. The mice were vaccinated with soluble Leishmania antigens (SLA) alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Guérin (BCG) vaccine and artemisinin alone on day 0 and boosted on day 13, then challenged with Leishmania major metacyclic promastigotes a week later. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring ex vivo lymphocyte proliferation and the production of interleukin (IL)-4, IL-5 and interferon gamma (IFN-γ) determined by flow cytometry. Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 (P0.05). Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad as compared to the collateral uninfected footpad. Subcutaneous administration of SLA + artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the unvaccinated mice (P>0.05), resulting in exacerbated disease. These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when administered with Leishmania antigens.