Evaluation of the adjuvanticity of artemisinin with soluble Leishmania major antigens in BALB/c mice

Albert Kimutai , Willy K. Tonui , Michael M. Gicheru , Peter Kamau Ngure , Johnstone Ingonga , Stella Kepha , Laban Ireri Njeru , Dorcas Wachira , Robert Karanja Muhia , Milkah Mwangi , Lydia B. Nyamwamu
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引用次数: 3

Abstract

Objective

To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice.

Methods

Seventy two female BALB/c mice were randomly assigned into six 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 and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin (IL)-4, IL-5 and gamma interferon (IFN-γ) determined by flow cytometry. 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 compared to the contralateral uninfected footpad.

Results

Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 (P < 0.05) and low levels of IFN-γ, resulting in exacerbated disease. In addition, 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 control unvaccinated mice (P > 0.05), resulting in exacerbated disease.

Conclusion

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 co-administered with Leishmania antigens.

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青蒿素对BALB/c小鼠可溶性利什曼原虫主抗原的佐剂性评价
目的研究青蒿素与可溶性利什曼抗原对BALB/c小鼠的佐剂作用。方法将72只雌性BALB/c小鼠随机分为6组。小鼠分别接种可溶性利什曼原虫抗原(SLA)、青蒿素与可溶性利什曼原虫抗原(SLA)、可溶性利什曼原虫抗原(SLA)和卡介苗(BCG)联合接种、青蒿素和卡介苗单独接种。未接种疫苗的小鼠作为对照组。通过测定体外淋巴细胞增殖和流式细胞术测定白细胞介素(IL)-4、IL-5和γ干扰素(IFN-γ)的产生,确定疫苗接种后细胞介导免疫的诱导。采用极限稀释法定量测定大螺杆菌感染足垫的寄生虫负荷,并测量感染足垫与对侧未感染足垫的病变大小,从而确定对大螺杆菌的保护作用。结果SLA +青蒿素组小鼠IL-4、IL-5水平显著升高(P <0.05)和低水平的IFN-γ,导致疾病加重。此外,皮下注射SLA +青蒿素、单独使用青蒿素或单独使用SLA可导致足垫肿胀和高寄生虫载量,与未接种疫苗的对照组小鼠相当(P >0.05),导致病情加重。结论青蒿素不适合作为利什曼原虫疫苗的佐剂。然而,由于青蒿素已被证明在体外和体内对利什曼原虫寄生虫有效,因此应进行进一步的研究,以确定其与利什曼原虫抗原共同施用时的免疫化疗潜力。
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