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*
Pasteur Institute of Brussels, Department of Virology, Brussels, Belgium;
Gesellschaft für Biotechnologische Forschung, Braunschweig, Germany; and
Merck Research Laboratories, West Point, PA 19486
Using culture filtrate Ag-specific mAbs generated from
mycobacteria-infected H-2b haplotype mice, we have
previously identified three genes in the Mycobacterium
tuberculosis genome, encoding proteins homologous to the
periplasmic ATP-binding cassette phosphate-binding receptor PstS
of the phosphate-specific transport system of E. coli.
To define the potential vaccinal properties of these phosphate-binding
proteins, female C57BL/6 mice were injected 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. challenge with M. tuberculosis H37Rv was analyzed.
Significant levels of highly Ag-specific Abs and Th1-type cytokines
IL-2 and IFN-
could be detected 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.
tuberculosis challenge, as compared with CFU counts in mice
vaccinated with control DNA. 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 screening of
potentially protective Ags from M. tuberculosis and that
the PstS-3 protein is a promising new subunit vaccine
candidate.
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