title: Intranasal vaccination with a double mutant of staphylococcal enterotoxin C provides protection against Staphylococcus aureus infection.
abstract: Staphylococcus aureus expresses a repertoire of factors including staphylococcal exotoxins (SEs), exoenzymes, and numerous cell-associated components that contribute to the pathogenesis of disease. We constructed and expressed a nontoxic double mutant SEC (dmSEC), devoid of superantigenic activity, and investigated the ability of intranasal vaccination with dmSEC plus cholera toxin (CT) adjuvant to protect mice against S. aureus infection. Mice were vaccinated with dmSEC and inoculated with a viable S. aureus clinical isolate strain. The survival rate in the immunized mice was higher, and bacterial counts in the organs were significantly lower than those in the control group. Intranasal vaccination with dmSEC induced the production of SEC-specific antibodies such as IgG1, IgG2b and IgA. dmSEC-vaccinated mice elicited significantly higher titers of interleukin-4 (IL-4) and IL-10, and lower levels of interferon-gamma (IFN-gamma) after challenge with S. aureus compared with the control group. Furthermore, the sera from dmSEC-immunized mice significantly inhibited IFN-gamma and tumor necrosis factor-alpha production in vitro. These results indicate that intranasal vaccination with dmSEC devoid of superantigenic properties induces systemic immune responses and provides protection against S. aureus infection.
authors.affiliation: Department of Microbiology and Immunology, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Hu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Omoe
authors.forename: Kouji
authors.initials: K
authors.lastname: Narita
authors.forename: Jing-Chun
authors.initials: JC
authors.lastname: Cui
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Shinagawa
authors.forename: Akio
authors.initials: A
authors.lastname: Nakane
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002478:Cells, Cultured; D004768:Enterotoxins / Q000235:genetics*; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013154:Spleen / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage* / Q000235:genetics*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology*; D018089:Superantigens / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D004768:Enterotoxins; D007106:Immune Sera; D013209:Staphylococcal Vaccines; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; C034959:enterotoxin C, staphylococcal; D007371:Interferon-gamma