02659nas a2200385   4500000000100000008004100001260001300042653002400055653001200079653002400091653002300115653001800138653002000156653000900176653000900185653002800194653004500222653002400267653002700291653002700318653001500345653001600360653001800376100001300394700001400407700001900421700001500440700001300455245011300468856007200581300001200653490000700665520158700672022001402259       2001                            d  c2001 Sep10aAmino Acid Sequence10aAnimals10aAntigens, Bacterial10aBacterial Vaccines10aBase Sequence10aCross Reactions10aFoot10aMice10aMolecular Sequence Data10aMycobacterium Infections, Nontuberculous10aMycobacterium bovis10aMycobacterium ulcerans10aSequence Analysis, DNA10aSkin Ulcer10aVaccination10aVaccines, DNA1 aTanghe A1 aContent J1 aVan Vooren J P1 aPortaels F1 aHuygen K00aProtective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC98650/pdf/ii005403.pdf  a5403-110 v693 a<p>Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep and necrotizing skin lesions, mostly on the arms and legs. Together with tuberculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and western Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protective role of the tuberculosis vaccine M. bovis BCG. To identify potential mechanisms for this cross-protection, we identified and characterized the M. ulcerans homologue of the important protective mycobacterial antigen 85 (Ag85A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the sequence from BCG. This antigen was sufficiently conserved to allow cross-reactive protection, as demonstrated by the ability of M. ulcerans- infected mice to exhibit strong cellular immune responses to both BCG and its purified Ag85 complex. To further address the mechanism of cross-reactive protection, we demonstrate here that prior vaccination with either BCG or plasmid DNA encoding BCG Ag85A is capable of significantly reducing the bacterial load in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Neelsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Together, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis, Buruli ulcer, and leprosy.</p>  a0019-9567