Intranasal immunization of BALB/c mice with enterotoxigenic Escherichia coli colonization factor CS6 encapsulated in biodegradable poly(DL-lactide-co-glycolide) microspheres

Intranasal immunization of BALB/c mice with enterotoxigenic Escherichia coli colonization factor CS6 encapsulated in biodegradable poly(DL-lactide-co-glycolide) microspheres
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DOI:
10.1016/j.vaccine.2005.09.024
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发表时间:
2006-02-27
期刊:
影响因子:
5.5
通讯作者:
Cassels, FJ
Cassels, FJ
中科院分区:
医学3区
文献类型:
--
作者:
Byrd, W;Cassels, FJ

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给小鼠鼻内施用封装在聚(DL)-丙交酯-共-乙交酯)微球(CS6-PLG)中的产肠毒素大肠杆菌定植因子CS6,测量免疫反应,并与类似施用的天然CS6和CS6加突变不耐热肠毒素粘膜佐剂(CS6 + mLT)的免疫反应进行比较。向小鼠鼻内施用天然CS6和CS6-PLG微球诱导血清IgG反应,其中CS6-PLG微球诱导比天然CS6显着更高(P<0.001)的反应。鼻内施用天然 CS6 后,没有测量到粪便 IgG 和 IgA 反应;然而,CS6-PLG 微球诱导的粪便 IgG 和 IgA 反应明显高于天然 CS6(P < 0.001)。与 CS6-PLG 微球相比,MLT 粘膜佐剂与 CS6 的共同给药诱导了显着更高的血清 (P < 0.001) 和粪便 (P < 0.01) 反应。然而,鼻内给予mLT佐剂后,小鼠表现出明显的痛苦迹象,表明对mLT有不良反应。因此,这引发了 MLT 的安全性及其作为鼻内佐剂的使用的问题。相比之下,鼻内施用的 PI-G 微球不会给小鼠带来明显的不适。本研究获得的结果表明,将 CS6 封装在 PLG 微球中,通过鼻内给予小鼠,起到增强 CS6 免疫反应的佐剂作用。由爱思唯尔有限公司出版
Mice were intranasally administered enterotoxigenic Escherichia coli colonization factor CS6 encapsulated in poly((DL)-lactide-co-glycolide) microspheres (CS6-PLG), with immune response measured and compared to that of similarly administered native CS6 and CS6 plus mutant heat-labile enterotoxin mucosal adjuvant (CS6 + mLT). Native CS6 and the CS6-PLG microspheres administered intranasally to mice induced serum IgG responses, with the CS6-PLG microspheres inducing a significantly greater (P < 0.001) response than native CS6. Following intranasal administration of native CS6, no fecal IgG and IgA responses were measured; however, the CS6-PLG microspheres induced significantly greater (P < 0.001) fecal IgG and IgA responses than native CS6. The coadministration of the mLT mucosal adjuvant with CS6 induced significantly greater serum (P < 0.001)and fecal (P < 0.01) responses than the CS6-PLG microspheres. However,following intranasal administration of the mLT adjuvant, the mice showed definite signs of distress, indicating an adverse reaction to the mLT. Thus, this brings into question the safety of the mLT and its use as an intranasal adjuvant. In contrast, the PI-G-microspheres administered intranasally caused no noticeable distress to the mice. The results obtained in this study indicate that the encapsulation of CS6 in PLG-microspheres administered intranasally to mice acted in an adjuvant capacity to enhance the CS6 immune response. Published by Elsevier Ltd.