特异性抗原融合蛋白结核病疫苗研究进展

Progress in specific antigen fusion protein in development of tuberculosis vaccine

结核病是一种严重危害人类健康的重大传染病,由于BCG预防效果不佳,研制新型结核病疫苗迫在眉睫。研究开发新型结核病疫苗应根据机体抗结核杆菌感染的免疫应答特点、结合BCG的不足来开展。新型结核病疫苗主要分为三类:重组BCG或重组结核菌;重组痘病毒或重组腺病毒载体疫苗;蛋白抗原亚单位或重组融合蛋白抗原亚单位疫苗。由于蛋白亚单位疫苗可以不受机体已被分枝杆菌刺激的影响,能特异性地诱导CD4+Th1细胞和CD8+细胞毒性T细胞活化,并且使用安全性好,而备受研究者的青睐。目前主要是以BCG或重组BCG初次免疫,然后选择亚单位疫苗加强免疫作为结核病疫苗序贯免疫策略。然而,单个蛋白制成亚单位疫苗,其免疫效果有限,因此将多个具有保护效果的抗原或多肽表达成融合蛋白,联合适当的佐剂,制成融合蛋白亚单位疫苗。目前,已有一些融合蛋白亚单位疫苗进入临床试验阶段,更多的融合蛋白正处于研究阶段。

Due to the poor effect of BCG , tuberculosis remains a leading infectious disease , it is a very urgent need to de-veloping a new tuberculosis （TB） vaccine.The research and development of new TB vaccines should be based on the char -acteristics of the body＆#39;s immune response against Mycobacterium tuberculosis infection, and help to overcoming the short-coming of BCG.New TB vaccines include the recombinant BCG or attenuated Mycobacterium tuberculosis, vaccinia virus or recombinant adenovirus used as carriers in the recombinant vaccines ,and the protein antigen or recombinant protein subunit vaccines .It is the protein subunit vaccine which can not be affected in the individual that has been stimulated by the myco -bacteria , so the specifically activation of CD 4＋Th1 cells and CD8＋CTL cells can be induced ,as well as good safety in use , thus this type of vaccine is widely focused by researchers .Current strategy for the vaccination is priming with BCG or re-combinant BCG followed by boosting with a subunit vaccine .However, the immune effect from a single protein subunit vac-cine is limited, so a fusion protein subunit vaccine with multiple protective antigens or peptides and accompanied by a suit -able adjuvant is developed .At present, some fusion protein subunit vaccines have been applied in clinical trials , and many are under research stage .