Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response

Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response
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DOI:
10.1016/j.vaccine.2007.05.042
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发表时间:
2007-08-29
期刊:
影响因子:
5.5
通讯作者:
Ali, Nahid
Ali, Nahid
中科院分区:
医学3区
文献类型:
--
作者:
Bhowmick, Sudipta;Ravindran, Rajesh;Ali, Nahid

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利什曼病影响着1200万人,人们普遍认为,接种疫苗是控制利什曼病的最佳长期战略。理想的疫苗应能有效预防和治疗利什曼病。然而,免疫学相关预测疫苗的效力和内脏利什曼病(VL)治疗的成功仍然不明确。在这里,我们将来自杜氏利什曼原虫前鞭毛体膜的可溶性利什曼原虫抗原(SLA)的疫苗效力与引发的免疫应答相关联,以预测疫苗在实验VL中的成功。免疫后产生IFN-γ和IL-4,Th 1应答占优势,是抗L. BALB/c小鼠感染杜氏杆菌。然后将最佳疫苗配方(带正电脂质体中的SLA)用于免疫治疗,该疫苗诱导肝脏和脾脏中超过10种寄生虫的清除。免疫治疗的成功表现出Th 1细胞因子、IFN-γ和IL-12激增的免疫调节,以及促进疾病的IL-4和IL-10的极端下调。这些发现表明,对Th 1的免疫调节对于成功的疫苗接种和免疫治疗都是有效的。(C)2007爱思唯尔有限公司保留所有权利。
Leishmaniasis affects 12 million people, and it is generally agreed that vaccination provides the best long-term strategy for its control. An ideal vaccine should be effective in both preventing and treating leishmaniasis. However, immunological correlates to predict vaccine efficacy and success of treatment in visceral leishmaniasis (VL) remain ill defined. Here, we correlated the vaccine efficacy of soluble leishmanial antigens (SLA) from Leishmania donovani promastigote membrane, entrapped in negative, neutral and positively charged liposomes with the elicited immune responses to predict vaccine success in experimental VL. Production of both IFN-gamma and IL-4 with a dominance of Th1 response following immunization was required for optimum success against L. donovani infection in BALB/c mice. The best vaccine formulation, SLA in positively charged liposomes, was then used for immunotherapy, This vaccine induced more than 10 elimination of parasites from both liver and spleen. The success of immunotherapy exhibited an immune modulation with surge in Th1 cytokines, IFN-gamma and IL-12 with extreme down regulation of disease promoting IL-4 and IL-10. These findings suggest that an immune modulation towards Th1 is effective for both successful vaccination and immunotherapy. (C) 2007 Elsevier Ltd. All rights reserved.