Development of StaphVAX™, a polysaccharide conjugate vaccine against S-aureus infection:: from the lab bench to phase III clinical trials

Staphylococcus aureus is the most common nosocomial pathogen and is responsible for approximately one-third of hospital-acquired bacteremias. The emergence of strains with multidrug resistance, including resistance to vancomycin, the antibiotic of last resort, presents the medical community with a major public health problem. Alternative therapies, including immunotherapy, have been in development for several decades. The discovery of S. aureus capsular polysaccharides from clinical isolates, and their importance to pathogenicity via antiphagocytic activity, opened a new window of opportunity for development of vaccines and immunotherapy against this pathogen. A conjugate vaccine, StaphVAX(TM) that includes the two most prevalent capsular polysaccharides, types 5 and 8, coupled to a carrier protein efficient in promoting a Th2 response, was developed. In a recent phase III clinical study in hemodialysis patients, StaphVAX(TM) was shown to prevent S. aureus bacteremia for up to 10 months following a single immunization. The history, epidemiology, serology, and development of StaphVAX(TM), including preclinical and clinical studies demonstrating efficacy are described in this review. (C) 2003 Elsevier Ltd. All rights reserved.