Bovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy. Augmentation of BCG with a subunit vaccine booster has been shown to increase protection but the selection of antigens has hitherto been left largely to serendipity. In the present study, we take a rational approach to identify the protective antigens of BCG, selecting a BCG transposon mutant library in naïve and BCG-vaccinated cattle. Ten mutants had increased relative survival in vaccinated compared to naïve cattle, consistent with loss of protective antigen targets making the mutants less visible to the BCG immune response. The immunogenicity of three putative protective antigens, BCG_0116, BCG_0205 (YrbE1B) and BCG_1448 (PPE20) was investigated using peptide pools and PBMCs from BCG vaccinated cattle. BCG vaccination induced PBMC to release elevated levels of IP10, IL-17a and IL-10 in response to all three antigens. Taken together, the data supports the further study of these antigens for use in subunit vaccines.

中文翻译：

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卡介苗接种保护性抗原靶点的基因筛选

牛结核病是一个重要的动物健康问题，也是全世界人畜共患结核病的主要原因。由于生产力的损失和控制程序的成本，它会导致严重的经济负担。引入有效的牛疫苗可以大大改善控制，但最有可能的候选疫苗 BCG 有几个局限性，包括可变效力。用亚单位疫苗加强剂增强 BCG 已被证明可以增加保护，但迄今为止抗原的选择主要是偶然的。在本研究中，我们采用合理的方法来鉴定 BCG 的保护性抗原，在幼稚和接种 BCG 的牛中选择 BCG 转座子突变文库。与未接种疫苗的牛相比，十个突变体在接种疫苗后的相对存活率有所提高，与保护性抗原靶点的丧失一致，使突变体对 BCG 免疫反应不那么明显。使用来自接种 BCG 的牛的肽库和 PBMC 研究了三种假定的保护性抗原 BCG_0116、BCG_0205 (YrbE1B) 和 BCG_1448 (PPE20) 的免疫原性。BCG 疫苗接种诱导 PBMC 释放升高水平的 IP10、IL-17a 和 IL-10，以响应所有三种抗原。总之，数据支持对这些抗原用于亚单位疫苗的进一步研究。IL-17a 和 IL-10 响应所有三种抗原。总之，数据支持对这些抗原用于亚单位疫苗的进一步研究。IL-17a 和 IL-10 响应所有三种抗原。总之，数据支持对这些抗原用于亚单位疫苗的进一步研究。