Horwitz Marcus A, Harth Günter
Department of Medicine, School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1688.
Infect Immun. 2003 Apr;71(4):1672-9. doi: 10.1128/IAI.71.4.1672-1679.2003.
Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, Mycobacterium bovis BCG, is urgently needed. We describe a recombinant BCG vaccine (rBCG30) expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis, the primary causative agent of TB, that affords greater survival after challenge than parental BCG in the highly demanding guinea pig model of pulmonary TB. Animals immunized with rBCG30 and then challenged by aerosol with a highly virulent strain of M. tuberculosis survived significantly longer than animals immunized with conventional BCG. The parental and recombinant vaccine strains are comparably avirulent in guinea pigs, as they display a similar pattern of growth and clearance in the lung, spleen, and regional lymph nodes. The pMTB30 plasmid encoding the 30-kDa protein is neither self-transmissible nor mobilizable to other bacteria, including mycobacteria. The pMTB30 plasmid can be stably maintained in Escherichia coli but is expressed only in mycobacteria. The recombinant and parental strains are sensitive to the same antimycobacterial antibiotics. rBCG30, the first vaccine against TB more potent than nearly century-old BCG, is being readied for human clinical trials.
结核病仍然是一个巨大的全球健康问题，迫切需要一种比目前效果不佳的牛分枝杆菌卡介苗（BCG）更有效的新型抗结核疫苗。我们描述了一种重组卡介苗疫苗（rBCG30），它表达并分泌结核分枝杆菌的30 kDa主要分泌蛋白，结核分枝杆菌是结核病的主要病原体。在要求极高的肺结核豚鼠模型中，rBCG30比亲本卡介苗在攻击后能提供更高的存活率。用rBCG30免疫然后经气溶胶感染高毒力结核分枝杆菌菌株攻击的动物，其存活时间明显长于用传统卡介苗免疫的动物。亲本疫苗株和重组疫苗株在豚鼠中具有相当的无毒力，因为它们在肺、脾和局部淋巴结中显示出相似的生长和清除模式。编码30 kDa蛋白的pMTB30质粒既不能自我传递，也不能转移到其他细菌，包括分枝杆菌。pMTB30质粒可以在大肠杆菌中稳定维持，但仅在分枝杆菌中表达。重组菌株和亲本菌株对相同的抗分枝杆菌抗生素敏感。rBCG30是第一种比近百年历史的卡介苗更有效的抗结核疫苗，正准备进行人体临床试验。
