title: Functionally inactive S. aureus alpha-toxin containing a single amino acid substitution: potential usefulness as a vaccine.
abstract: Substitution of His-35 with arginine in staphylococcal alpha-toxin leads to loss of its membrane perturbating properties in vitro. In this study, we report that the inactive mutant toxin is also devoid of toxic properties when injected intravenously into rabbits. Whereas a single application of native toxin at a dose of 20 micrograms/kg proved uniformly lethal within 3 hours (n = 3), all animals receiving 20, 100 or 200 micrograms/kg mutant toxin (n = 3 for each group) remained in unaltered, healthy states over a 15 day period of observation. Furthermore, all animals receiving inactive toxin developed antibody titers on day 10-15. No dose dependency was noted in the tested range. Thus, the site-directed alpha-toxin mutant (His-35:Arg) is an excellent vaccine candidate.
authors.affiliation: Institute for Medical Microbiology, University of Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
authors.forename: R
authors.initials: R
authors.lastname: Jursch
authors.forename: M
authors.initials: M
authors.lastname: Bröker
authors.forename: H
authors.initials: H
authors.lastname: Ronneberger
authors.forename: K D
authors.initials: KD
authors.lastname: Hungerer
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000276:immunology*; D001428:Bacterial Vaccines / Q000096:biosynthesis / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000276:immunology*; D006639:Histidine; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011817:Rabbits / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D006460:Hemolysin Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C021091:staphylococcal alpha-toxin; D006639:Histidine