Protective eff ect of intranasal vaccination with nontoxic mutant TSST-1 against Staphylococcus aureus infection

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Infection caused by methicillin-resistant Staphylococcus aureus （MRSA） has been the most commonlyacquired types of nosocomial infections. It was reported that anterior nares are the major reservoir of S. aureus andthe source of 80% of S. aureus bacteremia is endogenous. Considering these facts, elimination and reduction of nasalcarriage are thought to be eff ective protection against systemic S. aureus infection and nosocomial infection. Toxic shocksyndrome toxin 1（ TSST-1） is one of superantigens secreted by S. aureus. Previously, it was reported that mutant form（H135A） of TSST-1（ mTSST-1） was shown to be nontoxic, and subcutaneous vaccination with mTSST-1 could protectagainst systemic S. aureus infection in a mouse model. In this study, we investigated the protective eff ect of intranasalvaccination with mTSST-1 supplemented with non-toxic mutant（ H44A） Escherichia coli heat labile toxin（ mLT） as amucosal adjuvant. The results demonstrated that intranasal immunization with mTSST-1 plus mLT could efficientlyinduce production of anti-TSST-1 antibodies in sera and also induce anti-TSST-1 IgA production in bronchoalveolar lavagefl uids（ BALF） of vaccinated mice. In nasal-associated lymphoid tissues（ NALT） of vaccinated mice, anti-TSST-1 IgAsecreting cells were signifi cantly increased. To evaluate of the protective eff ect of this vaccine against systemic S. aureusinfection, BALB/c mice were vaccinated with mTSST-1 plus mLT and challenged with clinical isolated S. aureus 834intravenously. Bacterial numbers in spleen and liver, and cumulative mortality rate of vaccinated mice were lower thanthose of control mice. We further developed a mouse model of nasal S. aureus colonization. S. aureus bacterial numbers innasal cavity of vaccinated mice were signifi cantly reduced compared with those of control mice. These results indicatethat intranasal immunization with mTSST-1 plus mLT is able to induce systemic and mucous immune responses and ofprovide protection against systemic S. aureus infection and nasal colonization.

弘前医学. 59(Suppl.), 2007, p.S227-S234

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  • 弘前医学

    弘前医学 59 (Supplement), S227-S234, 2007-11-29

    弘前大学大学院医学研究科・弘前医学会

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