Bhowmick Sudipta, Ravindran Rajesh, Ali Nahid
Infectious Diseases Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
Vaccine. 2007 Aug 29;25(35):6544-56. doi: 10.1016/j.vaccine.2007.05.042. Epub 2007 Jun 8.
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 90% 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.
利什曼病影响着1200万人，人们普遍认为疫苗接种是控制该病的最佳长期策略。理想的疫苗应在预防和治疗利什曼病方面均有效。然而，用于预测内脏利什曼病（VL）疫苗疗效和治疗成功与否的免疫相关性仍不明确。在此，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）包裹于带负电、中性和带正电的脂质体中，将其疫苗效力与所引发的免疫反应相关联，以预测实验性VL中的疫苗接种效果。在BALB/c小鼠中，针对杜氏利什曼原虫感染取得最佳成功效果需要免疫后同时产生IFN-γ和IL-4且以Th1反应为主导。随后，将最佳疫苗制剂——带正电脂质体中的SLA用于免疫治疗。该疫苗使肝脏和脾脏中的寄生虫清除率超过90%。免疫治疗的成功表现为一种免疫调节，其中Th1细胞因子IFN-γ和IL-12激增，而促进疾病的IL-4和IL-10则极度下调。这些发现表明，向Th1方向的免疫调节对于成功的疫苗接种和免疫治疗均有效。
