Therapeutic Potential of a Candidate relA Deletion Mutant Vaccine of Mycobacterium Avium Subsp. Paratuberculosis

摘要

Analysis of the immune response to a mutant of Mycobacterium avium subsp. paratuberculosis with a deletion of relA (MapΔrelA) revealed that deletion of relA interrupts the pathways used by Map to subvert the immune response in goats and cattle to establish a persistent infection. The immune response elicited by MapΔrelA cleared infection and limited the capacity of wild type Map to establish an infection. The findings indicate the mutant should be useful as a vaccine under field conditions. The present study was conducted to explore the therapeutic potential of MapΔrelA using a cow with late stage paratuberculosis. The cow was tested negative using Map skin test and peripheral blood mononuclear cells were unresponsive to antigen stimulation ex vivo. A strong CD4 and CD8 proliferative response was detected one week post vaccination with MapΔrelA. Analysis of the cytokine profile for four weeks post vaccination revealed a mixed response with up–regulation of pro–inflammatory and inhibitory cytokine gene expression. The findings indicate further testing of the mutant as a candidate vaccine should include examining analysis of the cellular events associated with restoring a protective immune response as well as its therapeutic potential.