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Modulating the adjuvanticity of alum by co-administration of muramyl di-peptide (MDP) or Quil-A

机译:通过共同施用嘧啶二肽(MDP)或Quil-A来调节明矾的佐剂性

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摘要

The characterization of the immunological cascades of the innate immune system activated by pathogen associated molecular patterns (PAMP) recognized by pattern recognition receptors (PRR) have allowed the elucidation of the mechanisms underlying the immunomodulatory properties of adjuvants. Thus, the combinatorial use of adjuvants with specific, complementary functions is investigated to achieve tailored immune responses to subunit vaccines. We have previously shown how combinatorial administration of chitosan and cholera toxin B or muramyl-di-peptide (MDP) intranasally, but not intramuscularly, can allow small doses of MDP which, when administered alone cannot adjuvantise Helicobacter pylori urease (rUre), achieve an immunomodulatory effect through the specific physiological effect of chitosan. The aim of this study was to investigate if in the context of rUre the adjuvantising effect of MDP could be realized via the intramuscular route by combination with aluminium hydroxide, as compared with the routinely used veterinary adjuvant combination of alum and Quil-A. Serum IgG kinetics were comparable between the two adjuvant combination groups. However, the alum + MDP combination afforded higher antigen-specific recall responses in splenocyte cultures, associated with elevated release of the type I immune response cytokines IFN-gamma and IL-2. This data suggests that the adjuvanticity of MDP can be modulated in the context of alum in a manner dissimilar to that of Quil-A, achieving a balancing effect on the responses elicited by alum adjuvantisation.
机译:模式识别受体(PRR)识别的病原体相关分子模式(PAMP)激活的先天免疫系统的免疫级联的表征已阐明佐剂的免疫调节特性的机制。因此,研究了具有特定互补功能的佐剂的组合使用,以实现针对亚单位疫苗的定制免疫反应。先前我们已经证明了鼻内但不是肌肉内联合应用壳聚糖和霍乱毒素B或穆拉基二肽(MDP)可以允许小剂量的MDP,当单独施用时,它不能佐剂幽门螺杆菌脲酶(rUre)。通过壳聚糖的特定生理作用产生免疫调节作用。这项研究的目的是调查在常规情况下,与常规使用的明矾和Quil-A兽用佐剂相比,MDP的辅助作用是否可以通过肌内途径与氢氧化铝结合来实现。两种佐剂组合组的血清IgG动力学相当。然而,明矾+ MDP组合在脾细胞培养物中提供了更高的抗原特异性召回反应,与I型免疫应答细胞因子IFN-γ和IL-2释放的升高有关。该数据表明,可以在明矾的情况下以不同于Quil-A的方式调节MDP的佐剂,从而对明矾佐剂引发的反应达到平衡效果。

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