Staphylococcal
toxic shock syndrome toxin-1 (TSST-1), a superantigenic toxin produced by Staphylococcus (S.) aureus, is a major cause of
septic shock and
toxic shock syndrome. To investigate whether vaccination with a plasmid
DNA encoding a non-toxic mutant
TSST-1 (mTSST-1) can protect mice against wild-type TSST-1-induced lethal
shock, the mice were intranasally immunized with the plasmid
DNA (named pcDNA-mTSST-1) plus a mucosal adjuvant, a non-toxic mutant labile toxin (mLT). After the immunization, the mice were challenged with
TSST-1 and
lipopolysaccharide (LPS). The survival rate of mice immunized with pcDNA-mTSST-1 plus mLT was higher than that of the control mice immunized with PBS alone, mLT alone, pcDNA-mTSST-1 alone, or a parent plasmid plus mLT. The titers of
interferon-γ (IFN-γ) in the sera of mice immunized with pcDNA-mTSST-1 plus mLT were significantly lower than those of the mLT control mice. Immunization with pcDNA-mTSST-1 plus mLT increased the serum levels of TSST-1-specific
antibodies, especially
immunoglobulin G1 (
IgG1) and
IgG2a subclasses. Furthermore, the sera obtained from mice immunized with pcDNA-mTSST-1 plus mLT significantly inhibited the TSST-1-induced secretion of IFN-γ and
tumor necrosis factor-α (TNF-α) in murine spleen cells in vitro. These results indicate that immunization with pcDNA-mTSST-1 plus mLT provides protection against the lethal
toxic shock of mice induced by wild-type
TSST-1. The protective effect could be due to TSST-1-specific
neutralizing antibodies as well as the inhibition of IFN-γ and TNF-α secretions. Since
TSST-1 is commonly released by invasive S. aureus, the pcDNA-mTSST-1 should be useful in preventing toxin-induced
shock resulting from S. aureus
infection.