Pneumococcal vaccines: Current status and future perspectives

Streptococcus pneumoniae, a major causative bacterial pathogen of community-acquired pneumonia, possesses a thick polysaccharide capsule. Pneumococcal vaccination is recommended for elderly adults and patients with risk factors for pneumococcal infection. Host defenses against infection with S. pneumoniae include neutrophil-mediated opsonophagocytosis promoted by complements and antibodies. Current vaccines using capsular polysaccharides as antigens promote opsonophagocytosis by producing antibodies against the capsule, because S. pneumoniae inhibits complement activity. Currently, two types of vaccines are used in Japan, the 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13), which act via different immunological mechanisms. The antibody response generated by PPSV23 is classified as a thymus-independent response, which does not involve T cell help for activation of B cells and fails to induce memory B cell response. However, PCV13, which consists of pneumococcal polysaccharides conjugated to a carrier protein, elicits a thymus-dependent immune response, which induces affinity maturation of antibodies and differentiation of memory B cells through activation of helper T cells. These two vaccines are administered to elderly adults in Japan, although there as yet no clear standards as to how precisely the two vaccines should be used. Therefore, data collection on vaccine immunogenicity, efficacy, adverse effects, and cost-effectiveness are still under way. Serotype replacement, which is mainly caused by the expansion of non-vaccine serotypes, is becoming a clinical problem, because the current vaccines do not cover all serotypes of S. pneumoniae. Although the current pneumococcal vaccines continue to show good efficacy, this issue remains to be resolved. Therefore, development of universal vaccines that would work across serotypes is clinically desired. In this review, we summarize the current status and future perspectives of pneumococcal vaccine use.