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Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System

机译：包含分枝杆菌脂质的阳离子脂质体：新的强大的Th1佐剂系统。

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The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund's complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants. In this study, the immunostimulatory properties of a Mycobacterium bovis BCG lipid extract were tested for their adjuvant activity. Administration of the lipids in dimethyl dioctadecyl ammonium bromide-based cationic liposomes induced a powerful Th1 response characterized by markedly elevated antigen-specific immunoglobulin G2a (IgG2a) isotype antibodies and substantial production of gamma interferon. The adjuvant formulation (designated mycosomes) elicited high levels of gamma interferon both in C57BL/6 as well as in Th2-prone BALB/c mice. Furthermore, the mycosomes induced immune responses to protein antigens from several sources including Mycobacterium tuberculosis, Chlamydia muridarum, and tetanus toxoid. In a tuberculosis challenge model, the mycosomes combined with the Ag85B-ESAT-6 fusion protein were demonstrated to have a unique ability to maintain sustained immunological memory at a level superior to live BCG.
机译：分枝杆菌细胞壁提供的免疫刺激已经被使用了数十年，例如在弗氏完全佐剂中。最近，这种佐剂活性的潜在机制（包括Toll受体信号转导）已被弄清楚，证实了分枝杆菌成分可作为佐剂。在这项研究中，对牛分枝杆菌BCG脂质提取物的免疫刺激特性进行了佐剂活性测试。在基于二甲基二十八烷基溴化铵的阳离子脂质体中施用脂质诱导了强大的Th1反应，其特征在于抗原特异性免疫球蛋白G2a（IgG2a）同种型抗体显着升高，并且γ干扰素大量产生。佐剂制剂（称为真菌体）在C57BL / 6和Th2易感BALB / c小鼠中均引起高水平的γ干扰素。此外，真菌体还诱导了来自多种来源的对蛋白质抗原的免疫反应，这些来源包括：结核分枝杆菌，破壁衣原体和破伤风类毒素。在结核病挑战模型中，证明了结合Ag85B-ESAT-6融合蛋白的霉菌体具有独特的能力，可将持续的免疫记忆保持在优于活BCG的水平。

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