Rush C M, Hafner L M, Timms P
Centre for Molecular Biotechnology, School of Life Science, Queensland University of Technology, Brisbane, Australia.
J Med Microbiol. 1994 Oct;41(4):272-8. doi: 10.1099/00222615-41-4-272.
Many micro-organisms cause important diseases of the female genital tract. Because systematic vaccination does not usually provide a good immune response at mucosal sites, commensal lactobacilli from the female genital tract were developed as vehicles to deliver continued doses of foreign antigen directly to the genital mucosal surface with the aim of stimulating strong local mucosal immune responses. Lactobacilli were shown to be common inhabitants of the genital tract of the animal model studied, the guinea-pig. One species, Lactobacillus fermentum, was found in all guinea-pigs studied and was chosen for genetic manipulation. Improved methods of electroporation were developed to enable the routine transformation of L. fermentum BR11 strain with the broad host range plasmid pNZ17. This recombinantly modified Lactobacillus strain was shown to possess good segregational stability over 120 generations in the absence of antibiotic selection. When this recombinant L. fermentum strain was administered to the vaginal tract of three guinea-pigs it persisted for only 5 days. Despite the relatively short period of persistence in these initial experiments, this novel vaccine approach could provide an effective means of stimulating mucosal immunity in the female genital tract.
许多微生物会引发女性生殖道的重要疾病。由于系统性疫苗接种通常在黏膜部位无法产生良好的免疫反应，因此来自女性生殖道的共生乳酸杆菌被开发为载体，用于将持续剂量的外源抗原直接递送至生殖黏膜表面，目的是刺激强烈的局部黏膜免疫反应。乳酸杆菌被证明是所研究动物模型——豚鼠生殖道的常见栖居菌。在所研究的所有豚鼠中均发现了一种发酵乳杆菌，并选择其进行基因操作。开发了改进的电穿孔方法，以使发酵乳杆菌BR11菌株能够用广宿主范围质粒pNZ17进行常规转化。这种经重组修饰的乳酸杆菌菌株在无抗生素选择的情况下，在120代中显示出良好的分离稳定性。当将这种重组发酵乳杆菌菌株施用于三只豚鼠的阴道时，它仅持续了5天。尽管在这些初始实验中持续时间相对较短，但这种新型疫苗方法可能提供一种刺激女性生殖道黏膜免疫的有效手段。
