Strategies for and advances in the development of Staphylococcus aureus prophylactic vaccines

Abstract

Staphylococcus aureus is a common human commensal organism and also a major cause of nosocomial infections worldwide associated with high death rates, prolonged hospitalization and increased medical costs. Severe S. aureus infections are becoming progressively more difficult to treat because of the spread of strains resistant to antibiotics, and community-acquired disease is also increasing. There are many clinical presentations of disease including superficial skin and soft-tissue infections, as well as severe invasive infections including bacteremia, pneumonia and endocarditis. The diverse array of virulence factors expressed by S. aureus contributes to pathogenesis and has provided the basis for antigen selection for new vaccines in clinical development. Key prerequisites for vaccine development include the development of approaches to monitor the immunological responses generated by the vaccine in a way that can predict the vaccine effectiveness. Careful consideration of the patient populations in which candidate vaccines are initially evaluated for their efficacy will also play a key role for vaccine development. There are now several vaccines at different stages of clinical development that offer exciting prospects for the prevention of this devastating disease. The composition and the early clinical results from the evaluation of these vaccines are discussed in this article.

Keywords::

• clinical trial
• immune evasion
• Staphylococcus aureus
• vaccine development
• virulence factor

Acknowledgements

The authors would like to thank Dawn DeThomas for graphical assistance (Figure 1), Andreas Meinke at Intercell for providing Figure 2 and useful discussions, Kathrin U Jansen, Luke Handke, Robert Donald, Ingrid Scully, Alita miller, Bruce Green and Kena Swanson from Pfizer Vaccine Research for their thoughtful reviews and helpful comments regarding this manuscript.

Financial & competing interests disclosure

All authors are employees of Pfizer, Inc., NY, USA. Annaliesa S Anderson was employed by Merck Research laboratories 1998–2007 and holds stock in the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.