Advances in Pneumococcal Vaccines

Abstract

The introduction of Haemophilus influenzae type b (Hib) vaccine into the universal immunisation schedules of many industrialised countries and the subsequent remarkable decline in the incidence of invasive Hib disease has further highlighted the impact of invasive pneumococcal diseases. Streptococcus pneumoniae is now the leading cause of bacterial meningitis in children in many settings and a leading cause of vaccine-preventable bacterial disease in children worldwide. The currently marketed 23-valent pneumococcal polysaccharide vaccine provides large serotype coverage at a relatively low cost. However, it is not efficacious in young children. Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive disease in infants and young children, with favourable safety and immunogenicity profiles. These vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e. otitis media), nasopharyngeal acquisition of vaccine-specific serotypes of S. pneumoniae, and protection against pneumococcal disease caused by resistant strains. However, PCV contains a limited number of pneumococcal serotypes and, given adequate ecological pressure, replacement disease by non-vaccine serotypes remains a threat, particularly in areas with very high disease burden. Furthermore, 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. Therefore, monitoring disease burden and defining immune correlates of protection after widespread use of conjugate vaccines are crucial for the evaluation of these new generation vaccines. Furthermore, a need exists to develop pneumococcal vaccines with lower cost and larger serotype coverage. Development of one or more protein vaccines that might be easier and, thus, less expensive to manufacture, and which might provide protection against multiple serotypes, is in progress. This article reviews the current state of pneumococcal disease and pneumococcal vaccines in clinical use.