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脂质体作为变应性免疫疗法的载体

Liposomes as carriers for allergy immunotherapy.

作者信息

Audera C, Ramírez J, Soler E, Carreira J

机构信息

Alergia e Inmunología, Abelló S.A., Madrid, Spain.

出版信息

Clin Exp Allergy. 1991 Jan;21(1):139-44. doi: 10.1111/j.1365-2222.1991.tb00816.x.

Abstract

With the aim of obtaining an efficient but safer vaccine for allergy immunotherapy, the possibility of using liposomes as adjuvants has been considered given their proven low toxicity, adjuvant properties and ability to maintain the encapsulated substance in their interior for some time in vivo. Different methods of encapsulating allergenic extracts into neutral, positively, and negatively charged DPPC: cholesterol liposomes have been investigated and the immune response provoked by these in mice was studied and compared to the immune response to free allergen or other adjuvants such as aluminium hydroxide. The results obtained show that allergen encapsulated in all three types of liposomes elicit an increase in specific IgG levels higher than that provoked by free allergen, however, both encapsulation efficiency and specific IgG titre were higher when positively charged (DPPC: cholesterol stearylamine) liposomes were used. Specific IgE levels to allergen in positive and neutral liposomes was lower than to allergen in negative liposomes or adsorbed to Al(OH)3. No difference were found in the behaviour of liposomes prepared by different methods (the results were obtained from pooled sera from different groups of mice so there is no statistical data). These results confirm the immunoadjuvant effect of liposomes for allergy immunotherapy. Further studies to determine their lack of toxicity, pharmacokinetic studies and human clinical studies are necessary to confirm their adequacy for human use and advantage over current immunotherapy methods.

摘要

为了获得一种高效且更安全的过敏免疫治疗疫苗,鉴于脂质体已被证实具有低毒性、佐剂特性以及在体内能将包封物质在其内部维持一段时间的能力,人们考虑了将其用作佐剂的可能性。研究了将变应原提取物包封到中性、带正电和带负电的二棕榈酰磷脂酰胆碱:胆固醇脂质体中的不同方法,并研究了这些脂质体在小鼠体内引发的免疫反应,并与对游离变应原或其他佐剂(如氢氧化铝)的免疫反应进行了比较。所得结果表明,包封在所有三种类型脂质体中的变应原均能使特异性IgG水平升高,且高于游离变应原引发的水平,然而,当使用带正电的(二棕榈酰磷脂酰胆碱:胆固醇硬脂胺)脂质体时,包封效率和特异性IgG滴度均更高。阳性和中性脂质体中变应原的特异性IgE水平低于阴性脂质体中变应原或吸附于氢氧化铝上的变应原的特异性IgE水平。不同方法制备的脂质体在行为上未发现差异(结果来自不同组小鼠的混合血清,因此没有统计数据)。这些结果证实了脂质体在过敏免疫治疗中的免疫佐剂作用。有必要进一步开展研究以确定其无毒性、进行药代动力学研究和人体临床研究,以确认其适用于人体使用以及相对于当前免疫治疗方法的优势。

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