PNEUMOCOCCAL VIRULENCE FACTORS AND HOST IMMUNE-RESPONSES TO THEM

The principal virulence determinant of most encapsulated bacterial pat hogens is the possession of an extracellular capsule. This paper discu sses biological aspects of the Streptococcus pneumoniae capsule, putat ive roles played by accessory virulence factors of this pathogen and p rospects for improvement of the currently available pneumococcal vacci ne. Even though the interruption of genes encoding selected proteins h as been shown to attenuate virulence to some degree, the physical remo val of the pneumococcal capsule or the interruption of encapsulation g enes completely abolishes virulence in mice. The role of the capsule i n pathogenesis is not completely clear, however, since it is not known whether this structure is important in colonization, the obligatory f irst step in the process. In addition, a number of proteins have been implicated as possible accessory virulence factors. These include pneu molysin, 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 virule nce, 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 vaccine s, 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 i n small children.