PDF(Pubmed)
Abstract：
Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of Johne\'s disease (JD) in ruminants, establishes a prolonged and often lifelong enteric infection. The implementation of control measures for bovine JD has faced obstacles due to the considerable expenses involved in disease surveillance and hindered by unreliable and inadequate diagnostic tests, emphasizing the need for an effective vaccine that can stimulate mucosal immunity in the gastrointestinal tract. Previous investigations have demonstrated that deletion of the BacA gene in MAP produces an attenuated strain that can transiently colonize the calf small intestine while retaining its capacity to stimulate systemic immune responses similar to wildtype MAP strains. This study assessed the efficacy of the BacA gene deletion MAP strain, referred to as the BacA vaccine, when administered orally to young calves. The research aimed to evaluate its effectiveness in controlling MAP intestinal infection and to investigate the immune responses elicited by mucosal vaccination. The study represents the first evaluation of an enteric modified live MAP vaccine in the context of an oral MAP challenge in young calves. Oral immunization with BacA reduced MAP colonization specifically in the ileum and ileocecal valve. This partially protective immune response was associated with an increased frequency of CD4+ and CD8+ T cells with a pro-inflammatory phenotype (IFNγ+/TNFα+) in vaccinated animals. Moreover, re-stimulated PBMCs from vaccinated animals showed increased expression of IFNγ, IP-10, IL-2, and IL-17 at 10- and 12-weeks post challenge. Furthermore, immunophenotyping of blood leukocytes revealed that vaccinated calves had increased levels of T cells expressing cell-surface markers consistent with long-term central memory. Overall, our findings provide new insights into the development and immunogenicity of a modified live MAP vaccine against bovine JD, demonstrating oral vaccination can stimulate host immune responses that can be protective against enteric MAP infection.
摘要：
鸟分枝杆菌亚种。副结核病（MAP），反刍动物约翰病(JD)的病因，建立一个长期的，往往是终身的肠道感染。由于疾病监测涉及的大量费用，以及不可靠和不充分的诊断测试阻碍了对牛JD的控制措施的实施。强调需要一种能刺激胃肠道粘膜免疫的有效疫苗。先前的研究表明，MAP中BacA基因的缺失会产生一种减毒株，该减毒株可以瞬时定殖小牛小肠，同时保留其刺激类似于野生型MAP菌株的全身免疫反应的能力。这项研究评估了BacA基因缺失MAP菌株的功效，被称为BacA疫苗，当口服给小牛时。该研究旨在评估其在控制MAP肠道感染中的有效性，并研究通过粘膜疫苗接种引起的免疫反应。该研究代表了在小牛口服MAP攻击的背景下对肠道修饰的活MAP疫苗的首次评估。口服BacA免疫减少了MAP定植，特别是在回肠和回盲瓣中。这种部分保护性免疫应答与在接种动物中具有促炎表型(IFNγ+/TNFα+)的CD4+和CD8+T细胞的频率增加有关。此外，来自接种疫苗的动物的重新刺激的PBMC显示IFNγ的表达增加，挑战后10周和12周的IP-10、IL-2和IL-17。此外，血液白细胞的免疫表型分析显示，接种疫苗的小牛表达与长期中枢记忆一致的细胞表面标志物的T细胞水平升高。总的来说,我们的发现为针对牛JD的改良活MAP疫苗的开发和免疫原性提供了新的见解，证明口服疫苗可以刺激宿主免疫反应，可以保护免受肠道MAP感染。
