Parlane Natalie A, Denis Michel, Severn Wayne B, Skinner Margot A, Painter Gavin F, La Flamme Anne C, Ainge Gary D, Larsen David S, Buddle Bryce M
AgResearch, Hopkirk Research Institute, AgResearch Grasslands, Palmerston North, New Zealand.
Immunol Invest. 2008;37(2):129-42. doi: 10.1080/08820130701690782.
The development of defined sub-unit vaccines requires the inclusion in the vaccine of an immunological adjuvant. The most important property of adjuvants for vaccines aimed at inducing optimal protection against intracellular bacteria such as Mycobacterium tuberculosis or M. bovis is the ability to enhance cell-mediated immunity, specifically Th1 responses. In this paper, we describe a system where transgenic mice expressing a high proportion of T cells specific for an ovalbumin (OVA) peptide are used to assess the ability of a novel class of adjuvants to positively modulate cell-mediated immune responses. Defined fractions containing purified native or synthetic phosphatidylinositol mannosides (PIMs) from mycobacteria were assessed for their adjuvant activities in response to the model antigen (OVA). Purified PIM preparations given to mice with OVA by the subcutaneous route were shown to elicit an enhanced release of interferon-gamma (IFN-gamma) in cellular responses to OVA peptide in vitro. Very little interleukin-4 (IL-4) was released by cells from mice immunized with PIMs and OVA, whereas cells from animals immunized with complete Freund's adjuvant (CFA) and OVA released IL-4 as well as IFN-gamma. Synthetic preparations of PIM2 and PIM4 also acted as adjuvants in the mouse model studied. In addition, PIM preparations were shown to generate an efficient cell-mediated immune response to OVA, when the antigen/adjuvant preparations were administered via the oral route or intranasal route. PIM preparations elicited substantial release of interleukin-12 (IL-12) from dendritic cells (DCs). These data suggest that purified or synthetic PIMs act as adjuvants when administered at mucosal surfaces and represent a new class of adjuvants for mucosal immunization against intracellular pathogens.
确定亚单位疫苗的研发需要在疫苗中加入免疫佐剂。对于旨在诱导针对细胞内细菌（如结核分枝杆菌或牛分枝杆菌）的最佳保护的疫苗而言，佐剂的最重要特性是增强细胞介导免疫的能力，特别是Th1反应。在本文中，我们描述了一个系统，其中表达高比例针对卵清蛋白（OVA）肽的T细胞的转基因小鼠用于评估一类新型佐剂对细胞介导免疫反应进行正向调节的能力。评估了含有来自分枝杆菌的纯化天然或合成磷脂酰肌醇甘露糖苷（PIM）的特定组分对模型抗原（OVA）的佐剂活性。皮下给予OVA的小鼠纯化PIM制剂，在体外对OVA肽的细胞反应中可引发干扰素-γ（IFN-γ）释放增强。用PIM和OVA免疫的小鼠细胞释放的白细胞介素-4（IL-4）很少，而用完全弗氏佐剂（CFA）和OVA免疫的动物细胞释放IL-4以及IFN-γ。PIM2和PIM4的合成制剂在研究的小鼠模型中也起到佐剂作用。此外，当通过口服途径或鼻内途径给予抗原/佐剂制剂时，PIM制剂显示出对OVA产生有效的细胞介导免疫反应。PIM制剂从树突状细胞（DC）引发大量白细胞介素-12（IL-12）释放。这些数据表明，纯化或合成的PIM在粘膜表面给药时可作为佐剂，并且代表了一类用于针对细胞内病原体进行粘膜免疫的新型佐剂。
