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Vaccination with plasmid DNA encoding Ag85A from  M. bovis  BCG can partially protect C57BL/6 mice against a subsequent footpad challenge with  M. ulcerans . Unfortunately, this cross-reactive protection is insufficient to completely control the infection. Although genes encoding Ag85A from  M. bovis  BCG (identical to genes from  M. tuberculosis ) and from  M. ulcerans  are highly conserved, minor sequence differences exist, and use of the specific gene of  M. ulcerans  could possibly result in a more potent vaccine. Here we report on a comparison of immunogenicity and protective efficacy in C57BL/6 mice of Ag85A from  M. tuberculosis  and  M. ulcerans , administered as a plasmid DNA vaccine, as a recombinant protein vaccine in adjuvant or as a combined DNA prime-protein boost vaccine. All three vaccination formulations induced cross-reactive humoral and cell-mediated immune responses, although species-specific Th1 type T cell epitopes could be identified in both the NH 2 -terminal region and the COOH-terminal region of the antigens. This partial species-specificity was reflected in a higher—albeit not sustained—protective efficacy of the  M. ulcerans  than of the  M. tuberculosis  vaccine, particularly when administered using the DNA prime-protein boost protocol.

plos neglected tropical diseases

Improved Protective Efficacy of a Species-Specific DNA Vaccine Encoding Mycolyl-Transferase Ag85A from Mycobacterium ulcerans by Homologous Protein Boosting