Skinner Margot A, Buddle Bryce M, Wedlock D Neil, Keen Denise, de Lisle Geoffrey W, Tascon Ricardo E, Ferraz Jose Candido, Lowrie Douglas B, Cockle Paul J, Vordermeier H Martin, Hewinson R Glyn
AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand.
Infect Immun. 2003 Sep;71(9):4901-7. doi: 10.1128/IAI.71.9.4901-4907.2003.
The variable efficacy of bacillus Calmette-Guérin (Mycobacterium bovis BCG) in protecting humans and cattle against tuberculosis has prompted a search for a more effective vaccination regimen. A prime-boost strategy was investigated in cattle naturally sensitized to environmental mycobacteria by using a combination of three DNA vaccines coding for Hsp 65, Hsp 70, and Apa for priming, followed by a boost with BCG prior to experimental challenge with virulent M. bovis. Controls were vaccinated with DNA or BCG alone or were not vaccinated. The immune responses were monitored throughout the study, and protection was assessed based on reductions in the numbers of lesions and viable mycobacteria in lymph node samples. Vaccination with BCG alone or with a DNA prime-BCG boost regimen induced high levels of antigen-specific gamma interferon (IFN-gamma) in whole-blood cultures. In the prime-boost group there were fewer animals with severe lung lesions, fewer lymph nodes with lesions per animal, a smaller proportion of animals with lesions, lower mean lung and lymph node lesion scores, and less M. bovis isolated from retropharyngeal and thoracic lymph nodes compared to the results obtained for the nonvaccinated animals. The prime-boost regimen induced significant enhancement of protection in six parameters, compared with significant enhancement of protection in only two parameters for BCG alone. In addition, following challenge, in vitro IFN-gamma responses against ESAT-6 and CFP-10, as well as bovine tuberculin-induced skin test and in vitro IFN-gamma responses, were identified as immunological markers that predicted protection. The use of the prime-boost strategy suggested that a combination of vaccines may be better than a single vaccine for protection against tuberculosis.
卡介苗（牛分枝杆菌卡介苗）在保护人类和牛免受结核病侵害方面效果不一，这促使人们寻找更有效的疫苗接种方案。通过使用三种编码Hsp 65、Hsp 70和Apa的DNA疫苗组合进行初免，随后在以强毒牛分枝杆菌进行实验性攻毒之前用卡介苗进行加强免疫，对自然感染环境分枝杆菌的牛进行了初免-加强策略的研究。对照组分别单独接种DNA疫苗或卡介苗，或不接种疫苗。在整个研究过程中监测免疫反应，并根据淋巴结样本中病变数量和活菌数量的减少来评估保护效果。单独接种卡介苗或采用DNA初免-卡介苗加强免疫方案均可在全血培养中诱导高水平的抗原特异性γ干扰素（IFN-γ）。与未接种疫苗的动物相比，初免-加强免疫组中出现严重肺部病变的动物较少，每只动物有病变的淋巴结较少，有病变的动物比例较小，肺部和淋巴结病变平均评分较低，从咽后和胸部淋巴结分离出的牛分枝杆菌也较少。与单独接种卡介苗仅在两个参数上显著增强保护效果相比，初免-加强免疫方案在六个参数上显著增强了保护效果。此外，攻毒后，针对ESAT-6和CFP-10的体外IFN-γ反应，以及牛结核菌素诱导的皮肤试验和体外IFN-γ反应，被确定为预测保护效果的免疫标志物。初免-加强策略的应用表明，联合疫苗在预防结核病方面可能比单一疫苗更好。
