TB Research Group, Animal Health Veterinary Laboratory Agency-Weybridge, Woodham Lane, Addlestone, Surrey KT15 3NB, UK.
Vaccine. 2011 Jul 26;29(33):5453-8. doi: 10.1016/j.vaccine.2011.05.057. Epub 2011 Jun 2.
Vaccination of cattle with Mycobacterium bovis Bacille Calmette-Guérin (BCG) can provide significant protection against bovine tuberculosis (TB). However, BCG vaccination sensitises animals to respond to the tuberculin skin-test. This provides a potential operational impediment to the use of BCG as a cattle vaccine since the tuberculin skin-test is the primary surveillance tool used by many countries with 'test and slaughter' control strategies. Currently, it is also unclear what BCG-induced skin-test conversion means in respects to BCG's protective immunity. In the current study we first investigated the duration of tuberculin skin-test sensitisation in calves neonatally vaccinated with BCG. BCG vaccination induced strong skin-test responses in calves during their first 6 months. However, a rapid decay in skin-test sensitivity was observed after this time. Between 6 and 9 months this represented a reduction from 80% to 8% of calves providing a positive response in the single intradermal comparative cervical tuberculin test at standard interpretation. We next investigated the relationship between BCG induced skin-test sensitivity and retention of protective immunity. Calves were neonatally vaccinated with BCG and subsequently divided into 2 groups based on retention or loss of tuberculin skin-test responses after 6 months. In contrast to their skin-test responsiveness, these vaccinates maintained their tuberculin specific IFN-γ blood responses. Moreover, irrespective of their pre-challenge skin-test responses, following M. bovis challenge both groups of BCG vaccinated calves demonstrated comparable levels of protection, as evidenced by reduced TB-associated pathology. Therefore, we have demonstrated that following neonatal BCG vaccination of cattle, tuberculin skin-test responder frequencies waned rapidly after 6 months but importantly, loss of skin-test sensitivity did not correlate with loss of protective immunity. These findings could have implications for the practical application of BCG based cattle vaccines.
牛型分枝杆菌卡介苗（BCG）的接种可为牛结核病（TB）提供显著保护。然而，BCG 接种会使动物对结核菌素皮肤试验产生敏感性。这对 BCG 作为牛疫苗的使用构成了潜在的操作障碍，因为结核菌素皮肤试验是许多采用“检测和扑杀”控制策略的国家使用的主要监测工具。目前，BCG 诱导的皮肤试验转化对 BCG 的保护性免疫意味着什么，这一点也不清楚。在本研究中，我们首先调查了新生牛接种 BCG 后结核菌素皮肤试验致敏的持续时间。BCG 接种在小牛的前 6 个月中引起强烈的皮肤试验反应。然而，在此之后，皮肤试验敏感性迅速下降。在 6 至 9 个月之间，这代表着在标准解释下，80%的小牛在单次皮内比较颈结核菌素试验中提供阳性反应的比例从 80%下降到 8%。接下来，我们研究了 BCG 诱导的皮肤试验敏感性与保护性免疫保留之间的关系。小牛在出生时接种了 BCG，然后根据 6 个月后保留或丧失结核菌素皮肤试验反应将其分为 2 组。与皮肤试验反应性相反，这些接种疫苗者保持了其结核菌素特异性 IFN-γ 血液反应。此外，无论其在挑战前的皮肤试验反应如何，在牛分枝杆菌挑战后，两组 BCG 接种的小牛都表现出相似水平的保护，这表现为 TB 相关病理的减少。因此，我们已经证明，在牛接种 BCG 后，在 6 个月后，结核菌素皮肤试验反应者的频率迅速下降，但重要的是，皮肤试验敏感性的丧失与保护性免疫的丧失无关。这些发现可能对基于 BCG 的牛疫苗的实际应用产生影响。
