Hogervorst E J, Schouls L, Wagenaar J P, Boog C J, Spaan W J, van Embden J D, van Eden W
Department of Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
Infect Immun. 1991 Jun;59(6):2029-35. doi: 10.1128/iai.59.6.2029-2035.1991.
Live recombinant vaccinia viruses, expressing antigens from pathogenic microorganisms, are studied for their use as vaccines designed for the protection against infectious diseases. Infections with these vaccinia virus recombinants, expressing proteins or epitopes from viruses, parasites, or bacteria, have resulted in the development of specific neutralizing antibodies or cytotoxic T lymphocytes. Here, we describe the generation of a recombinant vaccinia virus expressing the mycobacterial 65-kDa heat shock protein (HSP65). A vaccinia recombinant virus was constructed by placing the gene for the Mycobacterium bovis BCG HSP65 under control of a vaccinia virus promoter and inserting this mycobacterial gene in the thymidine kinase locus of the vaccinia virus genome. Mycobacterial HSP65 is a critical antigen in the autoimmune model of adjuvant arthritis induced in Lewis rats by the immunization with Mycobacterium tuberculosis. We report the induction of immunity directed to this mycobacterial HSP65 by testing for the presence of specific antibodies and T-cell proliferation. Furthermore, induction of such immunity resulted in a reduction of arthritis severity when given to rats before or, even more interestingly, during development of arthritis. Disease reduction was not found after administration of HSP65 in the absence of vaccinia virus as a vector when given during arthritis development. Therefore, recombinant vaccinia virus may offer new prospectives for specific intervention in autoimmunity.
表达致病微生物抗原的活重组痘苗病毒正在被研究，以用作预防传染病的疫苗。用这些表达病毒、寄生虫或细菌的蛋白质或表位的痘苗病毒重组体进行感染，已导致产生特异性中和抗体或细胞毒性T淋巴细胞。在此，我们描述了一种表达分枝杆菌65-kDa热休克蛋白（HSP65）的重组痘苗病毒的构建。通过将牛分枝杆菌卡介苗HSP65基因置于痘苗病毒启动子的控制之下，并将该分枝杆菌基因插入痘苗病毒基因组的胸苷激酶基因座，构建了一种痘苗重组病毒。分枝杆菌HSP65是用结核分枝杆菌免疫诱导的Lewis大鼠佐剂性关节炎自身免疫模型中的关键抗原。我们通过检测特异性抗体的存在和T细胞增殖来报告针对这种分枝杆菌HSP65的免疫诱导。此外，当在关节炎发生之前或更有趣的是在关节炎发生期间给予大鼠时，这种免疫诱导导致关节炎严重程度降低。在关节炎发生期间给予HSP65而没有痘苗病毒作为载体时，未发现疾病减轻。因此，重组痘苗病毒可能为自身免疫的特异性干预提供新的前景。
