乳酸乳球菌作为黏膜免疫活载体疫苗传递抗原的研究进展

乳酸菌是人和动物肠道内的常见细菌,被公认为安全级(generally recognized as safe,GRAS)微生物。近年来,对于乳酸菌作为宿主菌表达外源蛋白或抗原的研究取得了一定进展。乳酸乳球菌(Lactococcus lactis)是乳酸菌的代表菌种,以其生长迅速、易于操作等优点成为表达外源抗原,作为黏膜免疫活载体疫苗的理想菌株。随着对乳酸乳球菌基因工程的研究逐渐深入,已发展了一系列组成型和诱导型乳酸乳球菌表达系统以及蛋白定位系统。破伤风毒素片段C、布氏杆菌L7/L12蛋白等多种病原微生物抗原已成功在乳酸乳球菌中表达,并已证明部分重组乳酸乳球菌作为黏膜免疫疫苗可以同时刺激局部黏膜免疫应答和系统免疫应答。目前,如何使活载体乳酸乳球菌以最佳方式向黏膜免疫系统提呈抗原继而诱导有效免疫反应是该领域的研究热点,也是巨大挑战。实现外源抗原在乳酸乳球菌中的准确定位及与细胞因子的共表达是未来研究的重要方向之一。乳酸乳球菌作为黏膜免疫活载体疫苗传递外源抗原具有广阔的应用前景。

Progress on Lactococcus lactis expressing heterologous antigens as live mucosal vaccines

Lactic acid bacteria(LAB) are natural commensals of the gastro-intestinal tracts of humans and most animals.They are considered to be safe bacteria with a GRAS(generally regarded as safe) status.The studies on LAB as live vehicles for expression of heterologous proteins or antigens have gained great progress in the past decades.Lactococcus lactis,an important species of LAB,possesses many properties that make it an ideal candidate for expressing and delivering heterologous proteins.With the significant advances in the genetic study of LAB,a series of constitutive or inducible gene expression systems as well as protein targeting systems had developed in Lactococcus lactis.Several antigens of pathogenic microorganisms,such as C subunit of tetanus toxin(TTFC) and the Brucella abortus ribosomal protein L7/L12,were successfully expressed in Lactococcus lactis.And it was showed that the recombinant Lactococcus lactis were able to induce specific mucosal immune response.It will be a great challenge how to make the recombinant Lactococcus lactis present heterologous proteins to the mucosal immune system in an effective way and induce specific immune response.One of the important directions for the further scientific development in this field is exploring protein targeting system to express heterologous antigens in precise locations of Lactococcus lactis.Expressing the antigen and cytokine simultaneously in Lactococcus lactis is an attractive direction as well.Using recombinant Lactococcus lactis that present antigens as live mucosal vaccines provides an effective way to prevent microorganisms invading and shows a promising future.