Khajuria Anamika, Gupta Amit, Singh Surjeet, Malik Fayaz, Singh Jaswant, Suri K A, Satti N K, Qazi G N, Srinivas V K, Ella Krishna
Division of Pharmacology, Regional Research Laboratory (CSIR), Jammu 180001, India.
Vaccine. 2007 Mar 30;25(14):2706-15. doi: 10.1016/j.vaccine.2006.06.036. Epub 2006 Jul 10.
Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40 microg) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 microg/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too.
明矾作为疫苗佐剂已使用很长时间。然而,其作为疫苗佐剂在支持细胞介导的反应方面存在局限性。因此,一种来自胡黄连的新型植物产品RLJ-NE-299A因其免疫刺激活性而受到研究,探讨了其作为替代佐剂的潜力。为了与明矾的佐剂活性进行比较,在用含有乙肝表面抗原(HBsAg)并佐以RLJ-NE-299A和明矾的制剂免疫小鼠后,评估了抗原特异性免疫反应。在用HBsAg进行初次免疫2周后,佐剂RLJ-NE-299A显著上调了淋巴结细胞培养物中Th1细胞因子IL-2、IL-12、IFN-γ、TNF-α和Th2细胞因子IL-4的表达。此外,在用HBsAg/RLJ-NE-299A免疫的小鼠血清中,免疫球蛋白IgG2a(Th1)和IgG1(Th2)亚型的水平均显著升高。结果表明,RLJ-NE-299A具有增强细胞介导和体液免疫反应的强大潜力,并且能够维持总的抗原特异性抗体反应。此外,RLJ-NE-299A为增强CD4辅助细胞(Th1和Th2)和CD8细胞群体提供了信号,这可能对乙肝病毒疫苗接种具有重要意义。含有疫苗抗原(HBsAg)的不同剂量的RLJ-NE-299A(0.312 - 40微克)耐受性良好,在2.5微克/毫升时具有最佳的T细胞反应。不仅如此,该佐剂还能够诱导对HBsAg的细胞免疫反应,Th1和Th2细胞因子上调证明了这一点,这使得小鼠能够克服在其他无反应小鼠群体中使用明矾佐剂疫苗时遇到的对HBsAg的无反应性。该研究表明,HPLC标准化组分RLJ-NE-299A在改善和维持针对HBsAg的免疫状态方面是优于明矾的佐剂选择,并且也可能被证明是与其他疫苗抗原合用的有用佐剂候选物。