Immune response and protective efficacy of live attenuated Salmonella vaccine expressing antigens of Mycobacterium avium subsp. paratuberculosis against challenge in mice

Subhash Chandra, Syed M. Faisal, Jenn Wei Chen, Tsai Tzu Chen, Sean P. McDonough, Sen Liu, Maria A.S. Moreira, Bruce L. Akey, Chao Fu Chang, Yung Fu Chang

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic granulomatous enteritis in ruminants that leads to diarrhea and eventually death. Existing vaccines have proven useful in limiting disease progression but have not been effective in preventing infection. To address this problem we constructed an attenuated Salmonella (ΔyejE; ΔssaV) strain harboring a plasmid that expressed a fusion protein comprised of the Salmonella Type III secretion system (T3SS) effector SopE and MAP antigens (85A, 85B, SOD, 74F) and evaluated its potential as vaccine candidate against MAP infection in mice. Of various SopE-MAP fusion proteins analyzed, only SopE104-Ag85A C-terminal202-347-SOD N-terminal1-72-Ag85B C-terminal173-330 and SopE104-74F1-148+669-786were successfully expressed and secreted into culture media as revealed by western blot analysis. Mice immunized with attenuated Salmonella (ΔyejE; ΔssaV) harboring the SopE104-Ag85A C-terminal202-347-SOD N-terminal1-72-Ag85B C-terminal173-330 and SopE104-74F1-148+669-786plasmid generated a potent and long lasting Th1 response characterized by production of IFN-γ. The cytokine profile varied at various time points after immunization and challenge, which showed down regulation of Th2 cytokines (IL-4, IL-10) and up-regulation of proinflammatory cytokines (IL-12 and IL-17). Further, the immune response correlated with protection as revealed by reduced bacterial load and improved histopathology of spleen and liver, which showed fewer granulomas and lower numbers of acid-fast bacilli as compared to PBS controls. Interestingly, vaccination with antigens mixed with Ribi adjuvant (Agmix+Ribi) imparted better protection than the attenuated salmonella vectored vaccine. Thus, priming with a live recombinant Salmonella strain that secretes MAP antigens represents a promising approach that could lead to development of an efficacious and cost effective vaccine for Johne's disease.

原文English
頁(從 - 到)242-251
頁數10
期刊Vaccine
31
發行號1
DOIs
出版狀態Published - 2012 十二月 17

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 免疫學與微生物學 (全部)
  • 獸醫 (全部)
  • 公共衛生、環境和職業健康
  • 傳染性疾病

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