Hu K F, Lövgren-Bengtsson K, Morein B
Swedish University of Agricultural Sciences, College of Veterinary Medicine, Department of Veterinary Microbiology, Section of Virology, Box 585, BMC, S-751 23, Uppsala, Sweden.
Adv Drug Deliv Rev. 2001 Sep 23;51(1-3):149-59. doi: 10.1016/s0169-409x(01)00165-x.
The immunostimulating complex (ISCOM) is documented as a strong adjuvant and delivery system for parenteral immunization. Its effectiveness for mucosal immunization has also been proven with various incorporated antigens. Lövgren et al. were the first to demonstrate the capacity of influenza virus ISCOMs to induce mucosal immune response and protection after one comparatively low nasal dose. Further studies show that similar to Cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), ISCOMs break immunological tolerance and exert strong mucosal adjuvant activity, resulting in secretory IgA and systemic immune responses. Striking is the capacity of ISCOMs to induce CTL response also after nasal administration. In contrast to CT, ISCOMs initiate mucosal as well as systemic immune responses in an IL-12 dependent manner but independently of IL-4. The recombinant B subunit of cholera toxin (rCTB) was incorporated in the same ISCOM particle to explore symbiotic effects. The IgA response to rCTB in lungs was increased 100-fold when rCTB was administered nasally in ISCOMs and more than 10-fold in the remote mucosa of the genital tract. An enhanced IgA response to a passenger antigen OVA was recorded in the remote genital tract. After i.n. administration of the envelope proteins of respiratory syncytial virus in ISCOMs, high serum antibodies were induced, almost at the same levels as those following parenteral immunization and potent IgA responses were also evoked both at the local respiratory mucosa, and in the cases tested at the distant mucosae of the genital and intestinal tracts. Similar results have also been recorded with ISCOMs containing envelope proteins from Herpes simplex virus, Influenza virus and Mycoplasma mycoides. The mucosal targeting property of envelope proteins of RSV was utilized in an HIV-gp120 RSV ISCOM formulation. After nasal administration an enhanced mucosal IgA response to gp120 was observed in the female reproductive tract. In general, antigens derived from envelope viruses or cell membranes incorporated into ISCOMs retain their biological activity and conformation, encompassing the mucosal targeting and virus neutralizing properties.
免疫刺激复合物（ISCOM）被证明是一种用于肠胃外免疫的强效佐剂和递送系统。其对黏膜免疫的有效性也已通过多种掺入抗原得到证实。Lövgren等人首次证明了流感病毒ISCOM在相对低剂量鼻腔给药后诱导黏膜免疫反应和提供保护的能力。进一步研究表明，与霍乱毒素（CT）和大肠杆菌不耐热毒素（LT）类似，ISCOM打破免疫耐受并发挥强大的黏膜佐剂活性，从而产生分泌型IgA和全身性免疫反应。值得注意的是，ISCOM在鼻腔给药后也能诱导CTL反应。与CT不同，ISCOM以IL-12依赖但独立于IL-4的方式启动黏膜和全身性免疫反应。霍乱毒素的重组B亚基（rCTB）被掺入同一ISCOM颗粒中以探索共生效应。当rCTB以ISCOM形式鼻腔给药时，肺部对rCTB的IgA反应增加了100倍，在生殖道远端黏膜中增加了10倍以上。在生殖道远端记录到对乘客抗原OVA的IgA反应增强。在ISCOM中经鼻给药呼吸道合胞病毒的包膜蛋白后，诱导出高血清抗体，几乎与肠胃外免疫后的水平相同，并且在局部呼吸道黏膜以及在生殖道和肠道远端黏膜测试的病例中也引发了强效的IgA反应。含有单纯疱疹病毒、流感病毒和丝状支原体包膜蛋白的ISCOM也记录到了类似结果。RSV包膜蛋白的黏膜靶向特性被用于HIV-gp120 RSV ISCOM制剂中。鼻腔给药后，在女性生殖道中观察到对gp120的黏膜IgA反应增强。一般来说，掺入ISCOM的源自包膜病毒或细胞膜的抗原保留其生物活性和构象，包括黏膜靶向和病毒中和特性。
