结核病免疫机制及疫苗研究进展

结核病是一种棘手的重大传染病.虽然存在一些有一定疗效的治疗药物,亦有预防性疫苗--卡介苗(BCG);但结核病仍在世界范围流行,且发病率和病死率居高不下.结核病的免疫病理机制及疫苗研究近年来取得了一定的进展.结核分枝杆菌通过Toll样受体(TLR)等模式识别受体,激活巨噬细胞的天然免疫反应,清除细菌和调节获得性免疫反应....

Progress in immunology of tuberculosis and new vaccine development

Tuberculosis remains a leading infectious cause of morbidity and mortality worldwide despite the availability of the bacille Calmette Guérin(BCG) vaccine and chemotherapy.Progress has been made in understanding immuopathogenesis and vaccine development in recent years.Mycobacterium tuberculosis(Mtb) may activate innate immunity of macrophage by Toll-like receptors(TLRs) and other pattern recognition receptors(PRRs),which can eliminate the bacteria and regulate the acquired immune responses.Besides major histocompatibility complex(MHC) restricted CD4+ and CD8+ T cells,CD1-restricted T cells and γδT cells also take part in immune responses to Mtb infection.Memory T cells and regulatory T cells play a special role in regulating immune responses to mycobacterial infection.In view of poor BCG protective efficacy in adults,improved control of tuberculosis requires development of new and more effective vaccines.Various vaccine candidates including recombinant BCG,live-attenuated Mtb,and booster vaccines,such as recombinant modified vaccinia virus Ankara expressing Mtb antigen,nucleic acid vaccines,and subunit protein vaccines with novel adjuvants,are at different stages of development.One promising vaccine strategy is priming with BCG or BCG replacement vaccine followed by boosting with subunit vaccines.However,the vaccine strategy,optimal dose,route,frequency,and timing of the boost remain to be determined.The challenges facing tuberculosis vaccine development include a lack of immune markers for protection in humans,difficulty in prioritizing which candidates to move to clinical trials,shortage of clinical trial sites,lengthy time required for vaccine evaluation,and high cost.