ARS | Publication request: Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 8, 2011
Publication Date: April 19, 2012
Citation: Chen, J., Faisal, S.M., Chandra, S., Mcdonough, S.P., Moreira, M.A., Scaria, J., Chang, C., Bannantine, J.P., Akey, B., Chang, Y. 2012. Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model. Vaccine. 30(19):3015-3025.

Interpretive Summary: In this mouse vaccine study, three different mutant strains of Mycobacterium avium subsp. paratuberculosis (MAP), the agent that causes Johne’s disease, were constructed. Each mutant has a single gene deleted, but the rest of the bacterium is normal. These mutants can infect cells and stimulate the immune system, but they cannot survive or cause disease. These three mutants were tested in mice to see which would best inhibit growth of the challenge bacteria. It was discovered that the leuD gene mutant was the most readily killed in mice. But it was also the one that best inhibited growth of the challenge bacteria, suggesting it may be a protective vaccine, at least in mice. This information is most useful to scientists and research organizations around the world actively working to develop vaccine base control measures against Johne's Disease.

Technical 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-gamma production and significant protective efficacy in both the reduction of inflammation and clearance of acid-fast bacilli, as compared with the mock vaccinated group.