de Vries P, van Binnendijk R S, van der Marel P, van Wezel A L, Voorma H O, Sundquist B, Uytdehaag F G, Osterhaus A D
Department of Immunobiology, National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands.
J Gen Virol. 1988 Mar;69 ( Pt 3):549-59. doi: 10.1099/0022-1317-69-3-549.
Immune-stimulating complexes (iscoms), which have recently been shown to be highly effective for the antigenic presentation of membrane proteins of viruses, were prepared with affinity-purified fusion (F) protein of measles virus (MV), using an adaptation of the standard method for iscom preparation. Immunization of monkeys with the F iscom preparation induced biologically active anti-F protein antibodies as was shown in haemolysis inhibition and cell-cell fusion inhibition tests. A whole MV iscom preparation, which also contained the haemagglutinin protein, induced not only also haemolysis-inhibiting antibodies, but, in contrast to the F iscom preparation, also haemagglutination-inhibiting and virus-neutralizing antibodies. In addition the F iscom preparation was shown to activate measles virus-specific T cells in mice. This was demonstrated by the generation of an MV-specific delayed type hypersensitivity response in F iscom-immunized animals and by the isolation of T cell clones specific for MV F protein with the T helper phenotype. Vaccination of mice with MV iscom or F iscom protected them from MV-induced fatal encephalopathy. The data concerning the immunogenicity of MV proteins presented in iscoms are discussed in relation to their potential for the development of an inactivated measles vaccine.
免疫刺激复合物(iscoms)最近被证明对病毒膜蛋白的抗原呈递非常有效,它是采用麻疹病毒(MV)亲和纯化的融合(F)蛋白,通过改进iscom制备的标准方法制备而成。用F iscom制剂免疫猴子可诱导产生具有生物活性的抗F蛋白抗体,这在溶血抑制和细胞-细胞融合抑制试验中得到了证实。完整的MV iscom制剂,其中也含有血凝素蛋白,不仅诱导产生了溶血抑制抗体,而且与F iscom制剂相比,还诱导产生了血凝抑制抗体和病毒中和抗体。此外,F iscom制剂还被证明可激活小鼠体内的麻疹病毒特异性T细胞。这在F iscom免疫的动物中产生MV特异性迟发型超敏反应以及分离出具有T辅助细胞表型的MV F蛋白特异性T细胞克隆中得到了证实。用MV iscom或F iscom给小鼠接种疫苗可保护它们免受MV诱导的致命性脑病。文中讨论了iscom中呈现的MV蛋白的免疫原性数据与其在开发灭活麻疹疫苗方面的潜力之间的关系。