Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors

Using culture filtrate Ag-specific mAbs generated from mycobacteria-infecte d H-2(b) haplotype mice, we have previously identified three genes in the M ycobacterium tuberculosis genome, encoding proteins homologous to the perip lasmic ATP-binding cassette phosphate-binding receptor PstS of the phosphat e-specific transport system of E. coli. To define the potential vaccinal pr operties of these phosphate-binding proteins, female C57BL/6 mice were inje cted i.m. with plasmid DNA encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and immunogenicity and protective efficacy against i.v. ch allenge with M. tuberculosis H37Rv was analyzed. Significant levels of high ly Ag-specific Abs and Th1-type cytokines IL-2 and IFN-gamma could be detec ted following vaccination with each of the three genes. However, only mice vaccinated with PstS-3 DNA demonstrated significant and sustained reduction in bacterial CFU numbers in spleen and lungs for 3 mo after M. tuberculosi s challenge, as compared with CFU counts in mice vaccinated with control DN A, Vaccination with PstS-2 DNA induced a modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1 DNA was completely ineffective in reducing bacterial multiplication. In conclusion, our results indicate that DNA vaccination is a powerful and easy method for comparative screenin g of potentially protective Ags from M, tuberculosis and that the PstS-3 pr otein is a promising new subunit vaccine candidate.