Scheppler Lorenz, Vogel Monique, Zuercher Adrian W, Zuercher Michael, Germond Jacques-Edouard, Miescher Sylvia M, Stadler Beda M
Institute of Immunology and Allergology, Inselspital, 3010 Bern, Switzerland.
Vaccine. 2002 Jul 26;20(23-24):2913-20. doi: 10.1016/s0264-410x(02)00229-3.
Lactobacilli are considered to be safe organisms making them attractive as vehicles for oral vaccination. We report that Lactobacillus johnsonii (Lj) partially survived simulated gastric conditions in vitro, suggesting that it could be used as an oral vaccine delivery vehicle. In order to test this approach, we used the cell wall anchored proteinase PrtB, isolated from Lactobacillus delbrueckii subsp. bulgaricus as a model antigen. Using a new vector system, we demonstrated expression of both proteinase PrtB alone and a mimotope peptide derived from tetanus toxin integrated in the sequence of proteinase PrtB (TTmim-PrtB fusion protein) on the surface of Lj. Oral immunisation of mice with recombinant Lj, expressing the TTmim-PrtB fusion protein induced a systemic IgG response against Lj and recombinantly expressed proteinase PrtB but no antibody response against the tetanus toxin mimotope suggesting that the mimotope was not sufficiently immunogenic to induce an immune response. Interestingly, a proteinase PrtB specific fecal IgA response was also induced, indicating that the proteinase PrtB fusion protein expressed as a cell surface protein on Lj can induce both systemic and local mucosal immune responses.
乳酸杆菌被认为是安全的生物体,这使其作为口服疫苗的载体具有吸引力。我们报道约翰逊乳杆菌(Lj)在体外模拟胃环境中能部分存活,这表明它可作为口服疫苗递送载体。为了测试这种方法,我们使用了从德氏乳杆菌保加利亚亚种分离的细胞壁锚定蛋白酶PrtB作为模型抗原。使用一种新的载体系统,我们证明了蛋白酶PrtB单独以及整合在蛋白酶PrtB序列中的源自破伤风毒素的模拟表位肽(TTmim-PrtB融合蛋白)在Lj表面的表达。用表达TTmim-PrtB融合蛋白的重组Lj口服免疫小鼠,诱导了针对Lj和重组表达的蛋白酶PrtB的全身性IgG反应,但未诱导针对破伤风毒素模拟表位的抗体反应,这表明模拟表位的免疫原性不足以诱导免疫反应。有趣的是,还诱导了蛋白酶PrtB特异性粪便IgA反应,表明在Lj上作为细胞表面蛋白表达的蛋白酶PrtB融合蛋白可诱导全身性和局部黏膜免疫反应。