Pneumococcal pathogenesis and the role of basement membrane binding proteins in the penetration of epithelial barriers
Dr Anne Berry
- Start Date:
01 January 2002
Women and Children's Hospital, Adelaide, Australia
Streptococcus pneumoniae (the pneumococcus) is an important pathogen, causing life-threatening invasive diseases such as pneumonia, meningitis and bacteraemia, as well as less serious but highly prevalent infections such as otitis media and sinusitis. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Polyvalent pneumococcal vaccines based on purified capsular polysaccharides have been available for nearly two decades, but their clinical efficacy has been limited by poor immunogenicity in high risk groups (particularly young children). Furthermore, anti-polysaccharide antibodies confer a strictly serotype-specific protection and only 23 of the 90 known serotypes are covered by existing formulations. CPS-protein conjugate vaccines are currently being developed and a 7 valent vaccine was released in 2000. However again the protection afforded by such vaccines is still serotype-specific and because of the cost of producing conjugates, the number of types covered has been reduced. Thus, although these vaccines may provide improved protection, it is against a much more limited serotype range. In view of this, much recent attention has focused on the possibility of developing vaccines based on pneumococcal protein antigens common to all serotypes. Although many putative virulence proteins have been characterized, few studies have directly examined the mechanism by which pneumococci colonize and penetrate the epithelial barriers of the host. This project is aimed at addressing this deficiency. Understanding the mechanisms involved in colonization and penetration of the epithelium of the nasopharynx or lung may reveal new ways to prevent pneumococcal infection.