title: Vaccination with plasmid DNA encoding a mutant toxic shock syndrome toxin-1 ameliorates toxin-induced lethal shock in mice.
abstract: 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.
authors.affiliation: Department of Oncology Surgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Mao-Hui
authors.initials: MH
authors.lastname: Feng
authors.forename: Jing-Chun
authors.initials: JC
authors.lastname: Cui
authors.forename: Akio
authors.initials: A
authors.lastname: Nakane
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Hu
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000276:immunology*; D060467:Disease Resistance / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000276:immunology*; D009500:Neutralization Tests; D010957:Plasmids / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014611:Vaccination
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D007106:Immune Sera; D050505:Mutant Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D004247:DNA