Griffin J F T, Mackintosh C G, Rodgers C R
Disease Research Laboratory, Department of Microbiology & Immunology, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Vaccine. 2006 Feb 6;24(6):835-45. doi: 10.1016/j.vaccine.2005.07.033. Epub 2005 Jul 26.
Tuberculosis due to Mycobacterium spp. continues to represent a major threat to human and animal health, prompting the search for effective vaccines. We have previously reported a sequential prime and boost homologous vaccination regime, using live avirulent M. bovis bacille Calmette-Guerin (BCG) strain 1173P2, that can provide significant protection to red deer (Cervus elaphus) against virulent M. bovis infection. Here, we have investigated the influence of varying the time-periods during and following the vaccination regime on the subsequent outcome of disease following post-vaccination pathogen challenge. Deer vaccinated using the standard regime of BCG-prime (week 0) and BCG-boost (week 8) followed by M. bovis challenge (week 14-16) were highly protected, showing significant reductions in the incidence of M. bovis infection and tuberculous lesions, as well as reduced pathogen burdens in sentinel lymphatic tissues. Decreasing the time-period between primary and secondary immunisations from 8 to 4 weeks had no significant impact on the protective efficacy afforded by BCG vaccination, while increasing this period to 43 weeks largely ablated protection. Increasing the time-period between secondary immunisation and M. bovis challenge from 6 to 26 or 52 weeks also had no significant impact on protection, suggesting that an appropriately timed BCG prime-boost vaccination regime can establish long-lasting protective immunological memory in deer. Finally, increasing the time-period between virulent M. bovis challenge and the subsequent post-mortem examination of disease outcome indicated that - once vaccinated by the standard prime-boost regime - deer remain refractory to disease if challenged and maintained for up to 52 weeks, suggesting that vaccinated animals harbouring low numbers of virulent M. bovis organisms do not succumb to disease activation over time. These findings are discussed in relation to concurrent measurements of in vivo and ex vivo immunological markers of disease and protection, as well as the wider implications of a standardised vaccine regimen for practical use in animal health.
分枝杆菌属引起的结核病仍然是对人类和动物健康的重大威胁，这促使人们寻找有效的疫苗。我们之前报道了一种序贯初免和加强的同源疫苗接种方案，使用减毒活牛分枝杆菌卡介苗（BCG）菌株1173P2，该方案可为马鹿（Cervus elaphus）提供针对强毒牛分枝杆菌感染的显著保护。在此，我们研究了在疫苗接种方案期间及之后改变时间间隔对疫苗接种后病原体攻击后疾病的后续结果的影响。采用卡介苗初免（第0周）和卡介苗加强（第8周），随后进行牛分枝杆菌攻击（第14 - 16周）的标准方案接种的鹿受到了高度保护，牛分枝杆菌感染和结核病变的发生率显著降低，哨兵淋巴组织中的病原体负荷也有所减少。将初次和二次免疫之间的时间间隔从8周缩短至4周对卡介苗接种提供的保护效力没有显著影响，而将该间隔延长至43周则大大消除了保护作用。将二次免疫和牛分枝杆菌攻击之间的时间间隔从6周增加到26周或52周对保护也没有显著影响，这表明适时的卡介苗初免 - 加强疫苗接种方案可以在鹿体内建立持久的保护性免疫记忆。最后，延长强毒牛分枝杆菌攻击与随后疾病结果的尸检之间的时间间隔表明，一旦采用标准的初免 - 加强方案接种，鹿在受到攻击并维持长达52周的情况下仍对疾病具有抵抗力，这表明携带少量强毒牛分枝杆菌的接种动物不会随着时间的推移而因疾病激活而死亡。我们结合对疾病和保护的体内和体外免疫标志物的同步测量，以及标准化疫苗方案在动物健康实际应用中的更广泛意义，对这些发现进行了讨论。
