中文摘要：研究描述了一种SmPill (R)佐剂胶囊化在增强肠毒性大肠杆菌（ETEC）口服疫苗保护效率方面的效果。研究表明，SmPill (R)微球在室温和极端条件下贮存数月仍能维持ETEC定植因子抗原I (CFA/I)的抗原性和口服活α-半乳糖酰基鞘氨醇(alpha-GalCer)的免疫刺激活性。另外，在小肠pH 环境下，SmPill (R)微球核的内部结构和抗原释放特性不受影响。尽管如此，在极端条件下贮存数周后，在胃pH 环境下，SmPill (R)微球表面形态发生了变化，从而影响了抗原释放。在SmPill (R)微球核和肠衣之间加入一个Opadry (R)白色过滤涂层可以阻止SmPill (R)微球表面形态的这些变化。在这些情况下，即使在高温、高湿环境中仍然可以在胃pH的酸度条件下释放抗原保护作用。这些结果表明，SmPill (R)微球能够维持口服疫苗佐剂的稳定性。
外文摘要：Oral vaccines present an attractive alternative to injectable vaccines for enteric diseases due to ease of delivery and the induction of intestinal immunity at the site of infection. However, susceptibility to gastrointestinal proteolysis, limited transepithelial uptake and a lack of clinically acceptable adjuvants present significant challenges. A further challenge to mass vaccination in developing countries is the very expensive requirement to maintain the cold chain. We recently described the effectiveness of a Single Multiple Pill (R) (SmPill (R)) adjuvanted capsule approach to enhance the effectiveness of a candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine. Here it was demonstrated that this delivery system maintains the antigenicity of ETEC colonisation factor antigen I (CFA/I) and the immunostimulatory activity of the orally active alpha-Galactosylceramide (alpha-GalCer) adjuvant after storage of SmPill (R) minispheres under room temperature and extreme storage conditions for several months. In addition, the internal structure of the cores of SmPill (R) minispheres and antigen release features at intestinal pH were found to be preserved under all these conditions. However, changes in the surface morphology of SmPill (R) minispheres leading to the antigen release at gastric pH were observed after a few weeks of storage under extreme conditions. Those modifications were prevented by the introduction of an Opadry (R) White film coating layer between the core of SmPill (R) minispheres and the enteric coating. Under these conditions, protection against antigen release at gastric pH was maintained even under high temperature and humidity conditions. These results support the potential of the SmPill (R) minisphere approach to maintain the stability of an adjuvanted whole cell killed oral vaccine formulation.
外文关键词：Vaccine; Oral delivery; Adjuvant; Capsule; Stability study
作者：Longet, S; Aversa, V; O'Donnell, D; Tobias, J; Rosa, M; Holmgren, J; Coulter, IS; Lavelle, EC
作者单位：爱尔兰都柏林圣三一学院
期刊名称：INTERNATIONAL JOURNAL OF PHARMACEUTICS
期刊影响因子：4.24
出版年份：2017
出版刊次：12
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