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首页> 外文期刊>Vaccine >Lipid vesicle size of an oral influenza vaccine delivery vehicle influences the Th1/Th2 bias in the immune response and protection against infection
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Lipid vesicle size of an oral influenza vaccine delivery vehicle influences the Th1/Th2 bias in the immune response and protection against infection

机译：口服流感疫苗递送载体的脂质囊泡大小会影响免疫应答中的Th1 / Th2偏倚并防止感染

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Previous studies, using parenteral administration of antigen in lipid vesicles, have indicated a possible role for vesicle size in determining the Th1/Th2 bias of the resulting immune response. We have also demonstrated that the incorporation of bile salts into lipid vesicles (bilosomes) allows successful induction of mucosal and systemic immunity via the oral route. The following study was therefore carried out to determine whether size could also influence the Th1/Th2 bias in the immune response to bilosome entrapped influenza A antigen containing haemagglutinin administered by the oral route in the mouse and whether this could influence the disease process in the classical ferret model of disease. Consequently we produced two formulations of influenza A antigen entrapped in bilosomes: BV3 which contained a single population (range 10-100nm, Z-average diameter 250nm) and BV which had two populations (60-350 and 400-2500nm, Z-average 980nm). Following oral vaccination of BALB/c mice, BV was found to generate an immune response that had a significantly greater Th1 bias than BV3 as measured by serum IgG2a production and antigen-induced spleen cell IFN-gamma production. In the traditional infection challenge model (ferrets) vaccination with BV (large) vesicles resulted in greater protection in terms of symptom-score and a higher responder number. However, both oral vaccine formulations were an improvement on intramuscular administration in terms of higher antibody production, lower temperatures, and reduced symptoms over time, post-infection. The results presented here demonstrate that oral vaccine formulations can be physically modified to manipulate resultant immune responses following vaccination and consequently can be designed to enhance the effectiveness of candidate vaccine antigens.
机译：先前在肠胃外使用脂质囊泡中抗原的研究表明，囊泡大小在确定最终免疫反应的Th1 / Th2偏倚方面可能发挥作用。我们还证明了将胆汁盐掺入脂质囊泡（脂质体）可以通过口服途径成功诱导粘膜和全身免疫。因此，进行了以下研究，以确定大小是否也会影响小鼠经口腔途径给予的含胆汁凝集素的含胆汁凝集素A抗原的免疫应答中的Th1 / Th2偏倚，以及是否会影响经典方法中的疾病过程雪貂的疾病模型。因此，我们制备了两种包含在双体中的A型流感抗原制剂：BV3包含一个种群（范围10-100nm，Z平均直径250nm）和BV包含两个种群（60-350和400-2500nm，Z平均980nm） ）。口服BALB / c小鼠疫苗后，发现BV产生的免疫应答的Th1偏倚明显高于BV3（通过血清IgG2a产生和抗原诱导的脾细胞IFN-γ产生）。在传统的感染挑战模型（雪貂）中，对BV（大）囊泡进行疫苗接种可在症状评分和更高的反应者数量方面提供更好的保护。然而，两种口服疫苗制剂在肌肉内给药方面都具有更高的抗体产生，更低的温度以及感染后随时间减少症状方面的改进。此处显示的结果表明，口服疫苗制剂可以进行物理修饰，以控制疫苗接种后产生的免疫反应，因此可以设计成增强候选疫苗抗原的效力。

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