Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model

Authors

Jenn-Wei Chen, Cornell University, Ithaca
Syed M. Faisal, Cornell University, Ithaca
Subhash Chandra, Cornell University, Ithaca
Sean P. McDonough, Cornell University, Ithaca
Maria A.S. Moreira, Cornell University, Ithaca
Joy Scaria, Cornell University, Ithaca
Chao-Fu Chang, Central Taiwan University of Science and Technology, Taichung
J. P. Bannantine, USDA-ARS, National Animal Disease CenterFollow
Bruce Akey, Cornell University, Ithaca
Yung-Fu Chang, Cornell University, IthacaFollow

Document Type

Article

Date of this Version

2012

Citation

Vaccine 30 (2012) 3015–3025

doi:10.1016/j.vaccine.2011.11.029

Comments

2011 Elsevier Ltd. All rights reserved.

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 post challenge. In addition, vaccination with leuD mutant induced a high level of IFN-􏰀 production and significant protective efficacy in both the reduction of inflammation and clearance of acid-fast bacilli, as compared with the mock vaccinated group.