Pneumococcal virulence factors and host immune responses to them.

The principal virulence determinant of most encapsulated bacterial pathogens is the possession of an extracellular capsule. This paper discusses biological aspects of the Streptococcus pneumoniae capsule, putative roles played by accessory virulence factors of this pathogen and prospects for improvement of the currently available pneumococcal vaccine. Even though the interruption of genes encoding selected proteins has been shown to attenuate virulence to some degree, the physical removal of the pneumococcal capsule or the interruption of encapsulation genes completely abolishes virulence in mice. The role of the capsule in pathogenesis is not completely clear, however, since it is not known whether this structure is important in colonization, the obligatory first step in the process. In addition, a number of proteins have been implicated as possible accessory virulence factors. These include pneumolysin, two distinct neuraminidases, an IgA1 protease and two surface proteins, pspA and psaA. While interruption of the expression of some of these proteins examined to date has been shown to attenuate virulence, so far it has not proven possible to completely abolish virulence in this fashion. Proteinaceous accessory virulence factors may prove important to the development of second-generation pneumococcal vaccines, however. Pneumococcal and other proteins conjugated to pneumococcal polysaccharides are currently being evaluated as carriers in attempts to improve the immunogenicity of polysaccharide vaccines, primarily in small children.