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淋病奈瑟菌蛋白I在脂质体和复合物中递送的三种不同脂质佐剂作用下对小鼠的免疫原活性。

Immunogenic activity of gonococcal protein I in mice with three different lipoidal adjuvants delivered in liposomes and in complexes.

作者信息

Jiskoot W, Teerlink T, Van Hoof M M, Bartels K, Kanhai V, Crommelin D J, Beuvery E C

出版信息

Infect Immun. 1986 Nov;54(2):333-8. doi: 10.1128/iai.54.2.333-338.1986.

Abstract

For several reasons the major outer membrane protein from Neisseria gonorrhoeae (gonococcal protein [PI]) is an attractive component for a gonococcal vaccine. This paper describes the influence of two different physical forms of PI on its immunogenic activity. To this end PI was delivered in liposomes and in protein-detergent complexes. In both forms PI was present in a multimeric form. The liposomes were composed of phosphatidylcholine and cholesterol. The effect of dicetylphosphate as a negatively charged amphiphile and three lipoidal adjuvants was investigated. Two lipoidal adjuvants (Avridine and dimethyldioctadecylammoniumbromide) were positively charged amphiphiles, whereas the third one (tridecyl N-acetylmuramyl-L-alanyl-D-isoglutaminate) was neutral. The protein-detergent complexes were also tested in the presence of the lipoidal adjuvants and in an AlPO4-adsorbed form. The liposome preparations were characterized for their size, charge, and residual amount of detergent. The immunogenic activity of PI in all forms was tested in mice. The results of the antibody assays showed that PI in the liposomes was more immunogenic than PI in the complexes. A second dose with liposomes induced only a small booster effect, whereas such a dose with the complexes produced pronounced booster effects. The incorporation of the positively charged lipoidal adjuvants in the liposomes resulted in enhanced booster effects. The highest immunogenic activity of PI after two injections, however, was observed in the complexed form adsorbed to AlPO4.

摘要

由于多种原因,淋病奈瑟菌的主要外膜蛋白(淋球菌蛋白[PI])是淋球菌疫苗的一个有吸引力的成分。本文描述了PI的两种不同物理形式对其免疫原活性的影响。为此,PI以脂质体和蛋白质-去污剂复合物的形式递送。在这两种形式中,PI均以多聚体形式存在。脂质体由磷脂酰胆碱和胆固醇组成。研究了磷酸二鲸蜡酯作为带负电荷的两亲物和三种脂质佐剂的作用。两种脂质佐剂(吖啶和二甲基二十八烷基溴化铵)是带正电荷的两亲物,而第三种(十三烷基N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺)是中性的。蛋白质-去污剂复合物也在脂质佐剂存在下以及以吸附于磷酸铝的形式进行了测试。对脂质体制剂的大小、电荷和去污剂残留量进行了表征。在小鼠中测试了所有形式的PI的免疫原活性。抗体检测结果表明,脂质体中的PI比复合物中的PI更具免疫原性。脂质体的第二次给药仅诱导了较小的增强效应,而复合物的这种剂量则产生了明显的增强效应。在脂质体中加入带正电荷的脂质佐剂导致增强效应增强。然而,两次注射后PI的最高免疫原活性在吸附于磷酸铝的复合物形式中观察到。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cabe/260165/5f0db31e016e/iai00098-0071-a.jpg

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