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: Adam R Spaulding, Wilmara Salgado-Pabón, Joseph A Merriman, Christopher S Stach, Yinduo Ji, Aaron N Gillman, Marnie L Peterson, Patrick M Schlievert
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 209 Issue 12 Pg. 1955-62 (Jun 15 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24357631 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Antibodies, Bacterial
• Antibodies, Neutralizing
• Bacterial Toxins
• Cytotoxins
• Enterotoxins
• Staphylococcal Vaccines
• Superantigens
• Virulence Factors
• enterotoxin F, Staphylococcal
• enterotoxin B, staphylococcal
• enterotoxin C, staphylococcal

Topics

• Animals
• Antibodies, Bacterial (blood)
• Antibodies, Neutralizing (blood)
• Bacterial Toxins (immunology)
• Cytotoxins (immunology)
• Disease Models, Animal
• Endocarditis, Bacterial (immunology, prevention & control)
• Enterotoxins (immunology)
• Female
• Immunization, Passive
• Male
• Methicillin-Resistant Staphylococcus aureus (immunology)
• Pneumonia, Staphylococcal (immunology, prevention & control)
• Rabbits
• Staphylococcal Vaccines (immunology)
• Superantigens (immunology)
• Virulence Factors (immunology)