Hetzel C, Janssen R, Ely S J, Kristensen N M, Bunting K, Cooper J B, Lamb J R, Young D B, Thole J E
Department of Biology, Imperial College School of Medicine, London, United Kingdom.
Infect Immun. 1998 Aug;66(8):3643-8. doi: 10.1128/IAI.66.8.3643-3648.1998.
We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mycobacterium vaccae. The broader application of the system was analyzed by preparation of constructs containing peptide epitopes from a range of infectious agents and allergens. We report detailed characterization of the immunogenicity of one such construct, in which an epitope from the Der p1 house dust mite allergen was expressed in M. vaccae. The construct was able to stimulate T-cell hybridomas specific for Der p1, and it induced peptide-specific gamma interferon responses when used to immunize naive mice. This novel expression system demonstrates new possibilities for the use of mycobacteria as vaccine delivery vehicles.
我们基于将肽插入细菌超氧化物歧化酶分子的一个允许性环内，开发了一种新型表位递送系统。该系统能使两种分枝杆菌疫苗菌株，即牛分枝杆菌卡介苗（BCG）和母牛分枝杆菌中异源肽实现高水平表达。通过制备包含来自一系列传染原和变应原的肽表位的构建体，分析了该系统更广泛的应用。我们报告了其中一种构建体免疫原性的详细特征，该构建体中来自屋尘螨变应原Der p1的一个表位在母牛分枝杆菌中表达。该构建体能够刺激对Der p1特异的T细胞杂交瘤，并且当用于免疫未接触过抗原的小鼠时，它能诱导肽特异性γ干扰素应答。这种新型表达系统展示了将分枝杆菌用作疫苗递送载体的新可能性。
