Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer

Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep an d necrotizing skin lesions, mostly on the arms and legs. Together with tube rculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and we stern Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protecti ve role of the tuberculosis vaccine M. bovis BCG. To identify potential mec hanisms for this cross-protection, we identified and characterized the M. u lcerans homologue of the important protective mycobacterial antigen 85 (Ag8 5A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the se quence from BCG. This antigen was sufficiently conserved to allow cross-rea ctive protection, as demonstrated by the ability of M. ulcerans- infected m ice to exhibit strong cellular immune responses to both BCG and its purifie d Ag85 complex. To further address the mechanism of cross-reactive protecti on, we demonstrate here that prior vaccination with either BCG or plasmid D NA encoding BCG Ag85A is capable of significantly reducing the bacterial lo ad in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Ne elsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Toge ther, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis,: Buruli ulcer, and leprosy .