Lofthouse S A, Andrews A E, Elhay M J, Bowles V M, Meeusen E N, Nash A D
Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
Int J Parasitol. 1996 Aug-Sep;26(8-9):835-42. doi: 10.1016/s0020-7519(96)80052-x.
Successful vaccination against any potential pathogen is critically dependent on inducing an appropriate immune response. The pivotal role of cytokines in the immune response to vaccination suggests that non-protective responses or responses that exacerbate disease subsequent to infectious challenge may be the result of limiting or preferential production of one or a number of these mediators. This suggests that the use of recombinant cytokines as vaccine adjuvants may offer a mechanism whereby the magnitude and phenotype of the immune response to vaccination can be specifically modified. In mice, recombinant cytokines have been used extensively as therapeutics, while studies describing vaccine adjuvant activity are more limited. Recombinant (r) interleukin (IL)-1, IL-2 and interferon (IFN) gamma have been used primarily to enhance humoral responses with enhanced protection assessed where appropriate. Cytokine adjuvant studies in ruminants have been restricted to recombinant ovine (rov) and bovine (rbov) IL-1 and IL-2. In sheep, their application has been optimised with respect to dose, route of delivery and formulation, for induction of humoral and cell mediated immunity (DTH and cytotoxicity) to the model protein antigen (Ag) avidin. The level of adjuvant activity of IL-1 in particular compares favourably to that of a variety of other traditional and new chemical adjuvants and detailed analysis has indicated no adverse local or systemic side-effects. Recent studies in our laboratory demonstrating the effectiveness of rovIL-1 as an adjuvant in single and multi-component bacterial toxoid vaccines, and studies from other laboratories demonstrating the application of rbovIL-1 as an adjuvant for the response in cattle to live attenuated viral vaccines, suggest that rIL-1 may become the adjuvant of choice for diseases where protection is mediated by high levels of circulating antibody (Ab). With respect to helminth parasites, IL-1 may prove useful as a component of vaccines based on "hidden Ags" which rely on induction of Ab. Based on analysis in mouse models of helminth infection, other cytokines such as IL-4 and IL-10 may be appropriate for vaccines based on induction of mechanisms involved in natural immunity.
成功接种针对任何潜在病原体的疫苗关键取决于诱导适当的免疫反应。细胞因子在疫苗接种免疫反应中的关键作用表明，非保护性反应或在感染性攻击后加剧疾病的反应可能是一种或多种这些介质产生受限或优先产生的结果。这表明使用重组细胞因子作为疫苗佐剂可能提供一种机制，通过该机制可以特异性地改变疫苗接种免疫反应的强度和表型。在小鼠中，重组细胞因子已被广泛用作治疗剂，而描述疫苗佐剂活性的研究则较为有限。重组（r）白细胞介素（IL）-1、IL-2和干扰素（IFN）γ主要用于增强体液反应，并在适当情况下评估增强的保护作用。反刍动物的细胞因子佐剂研究仅限于重组绵羊（rov）和牛（rbov）IL-1和IL-2。在绵羊中，它们在剂量、给药途径和制剂方面的应用已得到优化，以诱导对模型蛋白抗原抗生物素蛋白的体液免疫和细胞介导免疫（迟发型超敏反应和细胞毒性）。特别是IL-1的佐剂活性水平与多种其他传统和新型化学佐剂相比具有优势，详细分析表明没有不良的局部或全身副作用。我们实验室最近的研究证明了rovIL-1作为单组分和多组分细菌类毒素疫苗佐剂的有效性，以及其他实验室的研究证明了rbovIL-1作为牛对减毒活病毒疫苗反应的佐剂的应用，这表明rIL-1可能成为由高水平循环抗体（Ab）介导保护的疾病的首选佐剂。对于蠕虫寄生虫，IL-1可能作为基于“隐蔽抗原”的疫苗的一个组成部分有用，这种疫苗依赖于抗体的诱导。基于蠕虫感染小鼠模型的分析，其他细胞因子如IL-4和IL-10可能适用于基于自然免疫相关机制诱导的疫苗。
