Pinto Rachel, Saunders Bernadette M, Camacho Luis R, Britton Warwick J, Gicquel Brigitte, Triccas James A
Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
J Infect Dis. 2004 Jan 1;189(1):105-12. doi: 10.1086/380413. Epub 2003 Dec 22.
We demonstrate that Mycobacterium tuberculosis that is unable to export the complex lipid phthiocerol dimycocerosate has a decreased capacity to replicate in mice and affords sustained protective immunity against M. tuberculosis infection Protection was significantly better than that provided by the existing vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), and this improved protective efficacy was maintained for at least 24 weeks after vaccination. Protection afforded by this attenuated strain coincided with a number of factors that were not associated with BCG vaccination: long-term persistence of the strain within the host, sustained and potent induction of antimycobacterial interferon-gamma-secreting cells equal to that induced by virulent M. tuberculosis, and elicitation of T cells recognizing dominant M. tuberculosis antigens absent from BCG. These results suggest that the BCG vaccine may be too attenuated to afford effective protective immunity against tuberculosis, and vaccine strains that can provide sustained delivery of mycobacterial antigens are promising antituberculosis vaccine candidates.
我们证明，无法输出复合脂质结核杆菌索状因子的结核分枝杆菌在小鼠体内的复制能力降低，并能提供针对结核分枝杆菌感染的持续保护性免疫。这种保护作用明显优于现有疫苗卡介苗（BCG），且在接种疫苗后至少24周内，这种增强的保护效力一直保持。这种减毒株提供的保护作用与一些与卡介苗接种无关的因素有关：该菌株在宿主体内长期持续存在，诱导产生抗分枝杆菌的γ干扰素分泌细胞的能力持续且强大，与强毒结核分枝杆菌诱导产生的相当，并且能引发识别卡介苗中不存在的结核分枝杆菌主要抗原的T细胞。这些结果表明，卡介苗可能减毒过度，无法提供有效的抗结核保护性免疫，而能够持续递送分枝杆菌抗原的疫苗菌株有望成为抗结核疫苗候选物。
