Confronting the pneumococcus: a target shift or bullet change?

Pneumococcal disease remains a major killer, despite several years of biomedical research and vaccine technology. The striking efficacy of a seven-valent pneumococcal conjugate vaccine in the US brings hope for the potential conquest of pneumococcal disease but there are still several obstacles in completing this conquest. Although capsular specific antibodies have been shown to be highly protective, it remains unclear what concentration of these serotype-specific antibodies protect against disease and more recently it has become clear that opsonic activity and avidity of these antibodies are more critical determinants of protection than concentration. During the last decade the immunogenicity and protective capacity of several pneumococcal proteins have been described in animal models and these are now being explored for the development of species-common protein based vaccines. Protein conjugate vaccines are no doubt a great new addition to our amarmatorium in the battle against pneumococcal disease but for several epidemiologic reasons the results from Northern California will not be applicable to most other parts of the world. The vaccine contains a limited number of pneumococcal serotypes and given adequate ecological pressure, replacement disease by non-vaccine serotypes remains a real threat, particularly in areas with very high disease burden. The development of new non-serotype-specific vaccine candidates should be encouraged. Defining immune correlates of protection is crucial for the evaluation of these new generation vaccines. As currently available diagnostic methods are poorly sensitive, the true burden of pneumococcal disease may not be revealed until there is a highly efficacious vaccine in widespread use.