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评价 ISCOM 疫苗用于黏膜免疫预防乙型肝炎。

Evaluation of ISCOM vaccines for mucosal immunization against hepatitis B.

机构信息

Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar - 470 003, Madhya Pradesh, India.

出版信息

J Drug Target. 2010 May;18(4):282-91. doi: 10.3109/10611860903450015.

DOI:10.3109/10611860903450015
PMID:19958131
Abstract

Immune stimulating complexes (ISCOMs) incorporating recombinant hepatitis B surface antigen (HBsAg) was prepared for induction of humoral, cellular and mucosal immunity by intranasal administration. Prepared ISCOMs were characterized for its size, shape, incorporation efficiency, zeta potential, and antigen integrity. Designed ISCOMs possessed negative zeta potential (-21.7 mV) and an average size of 44.1 nm with antigen incorporation efficiency approximately 39 %. Serum anti-HBsAg IgG titer after three high nasal doses of ISCOMs was comparable with titer recorded after alum-HBsAg administered subcutaneously. Similarly, modest but higher cellular response (cytokines level in spleen homogenates) and significantly higher secretory sIgA response in mucosal secretions was observed (P < 0.001) in case of HBsAg ISCOM vaccines. Whereas, alum-HBsAg vaccine did not elicit considerable cellular or mucosal response. Thus, ISCOMs produced humoral, mucosal, and cellular immune responses upon nasal administration although high and multidose administrations were required to elicit potent immune responses. These data demonstrate potential of ISCOMs in their use as a carrier adjuvant for nasal subunit vaccines against hepatitis B.

摘要

免疫刺激复合物(ISCOMs)结合重组乙型肝炎表面抗原(HBsAg),通过鼻腔给药诱导体液、细胞和黏膜免疫。制备的 ISCOMs 进行了大小、形状、包封效率、ζ电位和抗原完整性的特征分析。设计的 ISCOMs 具有负的 ζ电位(-21.7 mV)和平均大小为 44.1nm,抗原包封效率约为 39%。三次高剂量鼻腔给予 ISCOMs 后,血清抗-HBsAg IgG 滴度与皮下给予铝佐剂-HBsAg 记录的滴度相当。同样,在 HBsAg ISCOM 疫苗中观察到适度但更高的细胞反应(脾匀浆中细胞因子水平)和黏膜分泌物中显著更高的分泌性 sIgA 反应(P<0.001)。然而,铝佐剂-HBsAg 疫苗没有引起相当的细胞或黏膜反应。因此,ISCOMs 经鼻腔给药可诱导体液、黏膜和细胞免疫应答,尽管需要高剂量和多次给药才能引发有效的免疫应答。这些数据表明 ISCOMs 有潜力作为乙型肝炎鼻用亚单位疫苗的载体佐剂。

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