Smith R E, Donachie A M, McLaren F H, Mowat A M
Department of Immunology, University of Glasgow, Western Infirmary, UK.
Immunology. 1998 Apr;93(4):556-62. doi: 10.1046/j.1365-2567.1998.00469.x.
Adjuvants are a critical component of non-viable vaccine vectors, particularly for those to be used via mucosal routes. Although most adjuvants act by inducing local inflammatory responses, the molecular basis of many of these effects is unclear. Here we have investigated whether interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) are required for the induction of local and systemic immune responses by oral and parenteral administration of ovalbumin (OVA) in immune stimulating complexes (ISCOMS), a potent mucosal adjuvant vector. Our results show that after oral or systemic immunization with OVA ISCOMS, IL-4 knockout (IL4KO) and IFN-gamma receptor knockout (IFN-gamma RKO) mice develop an entirely normal range of immune responses including delayed-type hypersensitivity (DTH), serum immunoglobulin G (IgG) antibodies, T-cell proliferation and cytokine production, class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) activity and intestinal IgA antibodies. These responses were of a similar magnitude to those found in the wild-type mice, indicating that the immunogenicity of ISCOMS is not influenced by the presence of IL-4 or IFN-gamma and emphasizing the potential of ISCOMS as widely applicable mucosal adjuvants.
佐剂是非活性疫苗载体的关键组成部分，对于那些通过黏膜途径使用的载体尤为重要。尽管大多数佐剂通过诱导局部炎症反应发挥作用，但其许多效应的分子基础尚不清楚。在此，我们研究了白细胞介素-4（IL-4）和干扰素-γ（IFN-γ）对于通过口服和肠胃外途径给予免疫刺激复合物（ISCOMS，一种有效的黏膜佐剂载体）中的卵清蛋白（OVA）诱导局部和全身免疫反应是否必要。我们的结果表明，在用OVA ISCOMS进行口服或全身免疫后，IL-4基因敲除（IL4KO）小鼠和IFN-γ受体基因敲除（IFN-γ RKO）小鼠产生了完全正常范围的免疫反应，包括迟发型超敏反应（DTH）、血清免疫球蛋白G（IgG）抗体、T细胞增殖和细胞因子产生、I类主要组织相容性复合体（MHC）限制的细胞毒性T淋巴细胞（CTL）活性以及肠道IgA抗体。这些反应的程度与野生型小鼠中的反应相似，表明ISCOMS的免疫原性不受IL-4或IFN-γ存在的影响，并强调了ISCOMS作为广泛适用的黏膜佐剂的潜力。
