title: Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model.
abstract: Johne's disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), results in serious economic losses worldwide especially in cattle, sheep and goats. To control the impact of JD on the animal industry, an effective vaccine with minimal adverse effects is urgently required. In order to develop an effective vaccine, we used allelic exchange to construct three mutant MAP strains, leuD, mpt64 and secA2. The mutants were attenuated in a murine model and induced cytokine responses in J774A.1 cell. The leuD mutant was the most obviously attenuated of the three constructed mutant strains. Our preliminary vaccine trial in mice demonstrated different levels of protection were induced by these mutants based on the acid-fast bacilli burden in livers and spleens at 8 and 12 weeks postchallenge. In addition, vaccination with leuD mutant induced a high level of IFN-γ production and significant protective efficacy in both the reduction of inflammation and clearance of acid-fast bacilli, as compared with the mock vaccinated group.
authors: Animal Health Diagnostic Center, Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors: Jenn-Wei
authors: JW
authors: Chen
authors: Syed M
authors: SM
authors: Faisal
authors: Subhash
authors: S
authors: Chandra
authors: Sean P
authors: SP
authors: McDonough
authors: Maria A S
authors: MA
authors: Moreira
authors: Joy
authors: J
authors: Scaria
authors: Chao-Fu
authors: CF
authors: Chang
authors: John P
authors: JP
authors: Bannantine
authors: Bruce
authors: B
authors: Akey
authors: Yung-Fu
authors: YF
authors: Chang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006836:Hydro-Lyases / Q000235:genetics; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016927:Mycobacterium avium subsp. paratuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D010283:Paratuberculosis / Q000517:prevention & control*; D013154:Spleen / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; C080865:MPB64 protein, Mycobacterium; D026901:Membrane Transport Proteins; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D000251:Adenosine Triphosphatases; C442123:SecA2 protein, Mycobacterium; D006836:Hydro-Lyases; C087070:leuD protein, Bacteria