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Comparison of the quality of protection elicited by toroid and peptideliposomal vaccine formulations against ricin as assessed by markers ofinflammation

机译:用炎症标志物评估环和肽脂质体疫苗制剂对蓖麻毒蛋白的保护作用的比较

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Ricin is a very toxic substance which inhibits protein synthesis and produces severe tissue damage and inflammation. It is very potent when inhaled as an aerosol and protection has been examined in a series of studies using vaccine candidates including a formaldehyde inactivated ricin toroid and the A chain of ricin, a polypeptide equivalent to half of the toxin molecule. Initially, subcutaneous injections of both compounds were found to protect against inhaled ricin but not without some subsequent adverse signs. Intra-pulmonary vaccination using liposomal formulations of these compounds was investigated with a view to improving lung condition following challenge. Using the humoral and local pulmonary immune responses as indices of vaccine performance, no significant difference between;een toroid or peptide vaccines was found. In the third and current study, the quality of lung protection by vaccines was assessed using markers of inflammation. Thus, the profiles of inflammatory cell and protein influx into the lung were determined following intratracheal (i.t,) challenge with ricin of rats treated with liposomal vaccine formulations. Results showed that liposomal ricin toroid offered a better quality of protection with a significantly lower influx of polymorphonuclear leucocytes (neutrophils) and little pulmonary oedema compared with the A chain/liposome formulation. Further, there was no significant difference between the quality of protection offered by the A chain when administered subcutaneously or locally into the lung by i.t. instillation. Liposomal ricin toroid is a good candidate vaccine and optimised pulmonary delivery by inhalation should be further examined. (C) 1999 Elsevier Science Ltd. All rights reserved. [References: 29]
机译:蓖麻毒素是一种剧毒物质,会抑制蛋白质合成,并导致严重的组织损伤和炎症。当以气雾剂形式吸入时,它非常有效,并已在一系列研究中使用候选疫苗进行了保护,这些候选疫苗包括甲醛灭活的蓖麻毒蛋白环氧化物和蓖麻毒蛋白A链(相当于毒素分子一半的多肽)。最初,发现两种化合物的皮下注射均可以防止吸入蓖麻毒蛋白,但并非没有随后的不良反应。为了改善挑战后的肺部状况,研究了使用这些化合物的脂质体制剂进行肺内疫苗接种。使用体液和局部肺部免疫应答作为疫苗性能的指标,未发现环型或肽类疫苗之间存在显着差异。在第三项和当前的研究中,使用炎症标志物评估了疫苗对肺的保护质量。因此,在用脂质体疫苗制剂治疗的大鼠的气管内(i.t)攻击蓖麻毒蛋白后,确定了炎症细胞和蛋白质向肺内的流入情况。结果表明,与A链/脂质体制剂相比,脂质体蓖麻毒蛋白环型提供更好的保护质量,多形核白细胞(嗜中性粒细胞)的流入明显减少,肺水肿小。此外,当通过皮下或局部皮下施用到肺中时,A链提供的保护质量之间没有显着差异。灌输脂质体蓖麻毒素环糊精是一种很好的候选疫苗,应进一步检查通过吸入优化的肺部递送。 (C)1999 Elsevier ScienceLtd。保留所有权利。 [参考:29]

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