title: Vaccination against Staphylococcus aureus pneumonia.
abstract: BACKGROUND
  Staphylococcus aureus causes serious infections in both hospital and community settings. Attempts have been made to prevent human infection through vaccination against bacterial cell-surface antigens; thus far all have failed. Here we show that superantigens and cytolysins, when used in vaccine cocktails, provide protection from S. aureus USA100-USA400 intrapulmonary challenge.
  
  
  METHODS
  Rabbits were actively vaccinated (wild-type toxins or toxoids) or passively immunized (hyperimmune serum) against combinations of superantigens (toxic shock syndrome toxin 1, enterotoxins B and C, and enterotoxin-like X) and cytolysins (α-, β-, and γ-toxins) and challenged intrapulmonarily with multiple strains of S. aureus, both methicillin-sensitive and methicillin-resistant.
  
  
  RESULTS
  Active vaccination against a cocktail containing bacterial cell-surface antigens enhanced disease severity as tested by infective endocarditis. Active vaccination against secreted superantigens and cytolysins resulted in protection of 86 of 88 rabbits when challenged intrapulmonarily with 9 different S. aureus strains, compared to only 1 of 88 nonvaccinated animals. Passive immunization studies demonstrated that production of neutralizing antibodies was an important mechanism of protection.
  
  
  CONCLUSIONS
  The data suggest that vaccination against bacterial cell-surface antigens increases disease severity, but vaccination against secreted virulence factors provides protection against S. aureus. These results advance our understanding of S. aureus pathogenesis and have important implications in disease prevention.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Spaulding
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Wilmara
authors.initials: W
authors.lastname: Salgado-Pabón
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Merriman
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stach
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine.
authors.forename: Yinduo
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis.
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Gillman
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Peterson
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D001427:Bacterial Toxins / Q000276:immunology; D003603:Cytotoxins / Q000276:immunology; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000517:prevention & control; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D007116:Immunization, Passive; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000276:immunology / Q000517:prevention & control*; D011817:Rabbits; D013209:Staphylococcal Vaccines / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D003603:Cytotoxins; D004768:Enterotoxins; D013209:Staphylococcal Vaccines; D018089:Superantigens; D037521:Virulence Factors; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal; C034959:enterotoxin C, staphylococcal
keywords: Staphylococcus aureus; cytolysins; endocarditis; pneumonia; superantigens; vaccination