Mutiso Joshua Muli, Macharia John Chege, Taracha Evans, Gicheru Michael Muita
Department of Tropical and Infectious Diseases, Institute of Primate Research, Karen, Nairobi 24481-00502, Kenya; ; Department of Zoological Sciences, Kenyatta University, Nairobi 43844-00100, Kenya.
J Biomed Res. 2012 Jan;26(1):8-16. doi: 10.1016/S1674-8301(12)60002-5.
In a previous immunogenicity and efficacy study in mice, montanide ISA 720 (MISA) was indicated to be a better adjuvant than bacillus calmette guerin vaccine (BCG) for a Leishmania vaccine. In the present study, we report the safety, immunogenicity and efficacy of Leishmania donovani (L. donovani) sonicated antigen delivered with alum-BCG (AlBCG), MISA or monophosphoryl lipid A (MPLA) in vervet monkeys following intradermal inoculums. Vaccinated and control animals were challenged with virulent L. donovani parasites and the parasitic burden was determined. Only animals vaccinated with alum-BCG adversely reacted to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric ANOVA followed by a post test showed significantly higher IgG antibodies, and revealed the presence of lymphoproliferative and interferon gamma responses in both AlBCG+Ag and MISA+Ag as compared to the MPLA+Ag or other groups (P < 0.001). We conclude that L. donovani sonicated antigen containing MISA is safe and is associated with protective immune response against Leishmania donovani infection in the vervet monkey model.
在之前一项针对小鼠的免疫原性和功效研究中,对于利什曼原虫疫苗而言,Montanide ISA 720(MISA)被证明是比卡介苗(BCG)更好的佐剂。在本研究中,我们报告了在黑长尾猴皮内接种含铝卡介苗(AlBCG)、MISA或单磷酰脂质A(MPLA)的杜氏利什曼原虫(L. donovani)超声抗原后的安全性、免疫原性和功效。对接种疫苗的动物和对照动物用强毒力的杜氏利什曼原虫寄生虫进行攻击,并测定寄生虫负荷。只有接种含铝卡介苗的动物对接种物产生了溃疡性红斑皮肤硬结的不良反应。非参数方差分析及后续检验显示,与MPLA+抗原组或其他组相比,AlBCG+抗原组和MISA+抗原组的IgG抗体显著更高,且存在淋巴细胞增殖和干扰素γ反应(P < 0.001)。我们得出结论,含MISA的杜氏利什曼原虫超声抗原是安全的,并且在黑长尾猴模型中与针对杜氏利什曼原虫感染的保护性免疫反应相关。