Vaccination against staphylococcus aureus pneumonia

Adam R. Spaulding, Wilmara Salgado-Pabón, Joseph A. Merriman, Christopher S. Stach, Yinduo Ji, Aaron N. Gillman, Marnie L. Peterson, Patrick M. Schlievert

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1955-1962
Number of pages8
JournalJournal of Infectious Diseases
Volume209
Issue number12
DOIs
StatePublished - Jun 15 2014

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (grant numbers AI074283, AI73366, and AI57153). P. M. S. is a member of the Great Lakes Regional Center of Excellence in Biodefense and Emerging Infectious Diseases.

Keywords

  • Staphylococcus aureus
  • cytolysins
  • endocarditis
  • pneumonia
  • superantigens
  • vaccination

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