Vaccination with Plasmid DNA Encoding a Mutant Toxic Shock Syndrome Toxin-1 Ameliorates Toxin-induced Lethal Shock in Mice

Vaccination with Plasmid DNA Encoding a Mutant Toxic Shock Syndrome Toxin-1 Ameliorates Toxin-induced Lethal Shock in Mice

MAO-HUI FENG,^1,3 JING-CHUN CUI,^2,3 AKIO NAKANE³ and DONG-LIANG HU^3,4

¹Department of Oncology Surgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, P.R. China
²Department of Bio-Engineering, Dalian Nationalities University, Dalian, Liaoning, P.R. China
³Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
⁴Department of Zoonoses, Kitasato University School of Veterinary Medicine, Towada, Aomori, Japan

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.

keywords —— infection; mucosal immunization; Staphylococcus aureus; superantigen; toxic shock syndrome toxin

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Tohoku J. Exp. Med., 2013, 231, 1-8

Correspondence: Dong-Liang Hu, Ph.D., Department of Zoonoses, Kitasato University School of Veterinary Medicine, 23-35-1, Higashi, Towada, Aomori 034-8628, Japan.

e-mail: hudl@vmas.kitasato-u.ac.jp