INRA, UMR1319 Micalis, Commensal and Probiotics-Host Interactions Laboratory, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
Microb Cell Fact. 2011 Aug 30;10 Suppl 1(Suppl 1):S4. doi: 10.1186/1475-2859-10-S1-S4.
Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials.
食用级别的乳酸菌（LAB）在发酵食品中已被人类安全食用了数个世纪。因此，它们是开发新型口服载体的良好候选物，构成了减毒病原体的有吸引力的替代品，可用于黏膜传递策略。在此，我们总结了迄今为止使用 LAB 作为治疗性蛋白质和 DNA 疫苗的黏膜传递载体的研究工作。我们的大部分工作都是基于模型 LAB 乳球菌乳球菌，为此我们开发了高效的遗传工具，包括表达信号和宿主菌株，用于治疗性蛋白质（如抗原、细胞因子和酶）的异源表达。由此产生的重组乳球菌菌株已在不同的动物模型中成功测试了其预防和治疗效果：i）针对小鼠中的人乳头瘤病毒 16（HPV-16）诱导的肿瘤，ii）部分预防小鼠中的牛β-乳球蛋白（BLG）过敏反应，iii）调节肥胖小鼠的体重和食物消耗。引人注目的是，近年来，我们实验室已成功地将所有这些工具转化到乳杆菌属。值得注意的是，构建并测试了具有抗氧化活性的干酪乳杆菌菌株，以应对两种化学诱导的结肠炎模型。与此同时，我们还开发了一种基于使用乳球菌在黏膜水平传递 DNA 的策略，并能够证明乳球菌能够通过 DNA 传递来调节宿主反应。今天，我们认为，我们所有一致的数据，以及其他小组获得的数据，都证明并加强了使用 LAB（特别是乳球菌和乳杆菌菌株）开发新型治疗性蛋白质黏膜传递载体的兴趣，这些载体现在应该在人类临床试验中进行测试。
