Cellular immunity to Streptococcus pneumoniae: implications for vaccine-mediated prevention

INTRODUCTION: Streptococcus pneumoniae asymptomatically colonizes the nasopharynx but can also cause mucosal infections or invasive pneumococcal disease. Despite the significant positive impact of pneumococcal conjugate vaccines, the burden of pneumococcal disease persists, reflecting the inherent limitations of a strategy that elicits serotype-dependent humoral immunity against a pathogen with > 100 known serotypes. AREAS COVERED: Animal model data suggest that in addition to anti-capsular antibodies, CD4+ T-cell responses (including Th1 and Th17) and CD8+ T cells may also contribute to protection against pneumococcal colonization and disease. However, the contribution of cellular immune responses against S. pneumoniae in humans has not been fully elucidated, with human challenge models suggesting a potential role for CD8+ T cells, CD4+ Th17 cells, and tissue-resident memory T cells in protection. We summarize here the evidence on cellular immune responses elicited by exposure to S. pneumoniae and provide an overview of the cellular immune responses induced by candidate pneumococcal vaccines (whole-cell vaccines, protein-based vaccines, and vaccines using MAPS technology). EXPERT OPINION: Improving protection against S. pneumoniae will require future pneumococcal vaccines to induce a broad, multipronged immune response. This strategy implies identifying new immunological benchmarks beyond capsular antibodies. Therefore, defining protective cellular responses represents a critical research priority.