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J Infect Dis. 2014 Jun 15;209(12):1955-62. doi: 10.1093/infdis/jit823. Epub 2013 Dec 19.

Vaccination against Staphylococcus aureus pneumonia.

Author information

1
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City.
2
Department of Veterinary Biosciences, College of Veterinary Medicine.
3
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis.

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.

KEYWORDS:

Staphylococcus aureus; cytolysins; endocarditis; pneumonia; superantigens; vaccination

PMID:
24357631
PMCID:
PMC4038136
DOI:
10.1093/infdis/jit823
[Indexed for MEDLINE]
Free PMC Article
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