Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design Principles

Streptococcus pneumoniae (the pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. Most isolates express a capsule, the species-wide diversity of which has been immunologically classified into ∼100 serotypes. Capsule polysaccharides have been combined into multivalent vaccines widely used in adults, but the T cell independence of the antibody response means they are not protective in infants. Polysaccharide conjugate vaccines (PCVs) trigger a T cell-dependent response through attaching a carrier protein to capsular polysaccharides. The immune response stimulated by PCVs in infants inhibits carriage of vaccine serotypes (VTs), resulting in population-wide herd immunity. These were replaced in carriage by non-VTs. Nevertheless, PCVs drove reductions in infant pneumococcal disease, due to the lower mean invasiveness of the postvaccination bacterial population; age-varying serotype invasiveness resulted in a smaller reduction in adult disease. Alternative vaccines being tested in trials are designed to provide species-wide protection through stimulating innate and cellular immune responses, alongside antibodies to conserved antigens.