Insights into the heterogeneity of pneumococcal polysaccharide vaccine immunogenicity in older adults

BACKGROUND: Older adults are at increased risk of pneumonia and invasive pneumococcal disease, yet vaccine-induced immunity varies substantially within this population. We evaluated antibody responses to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in 188 Dutch adults aged 72-79 years (trial number: NL74843.041.20; EudraCT: 2020-003620-16), with follow-up extending to two years post-vaccination.

RESULTS: Serotype-specific IgG and IgM concentrations increased significantly for all 23 serotypes and remained elevated after two years, compared to baseline. Opsonophagocytic activity, measured for serotypes 1, 3, 8 and 19A, correlated with IgG but not with IgM concentrations. Using AAAAI guidelines for evaluating pneumococcal vaccine responses in adults, 46.2% of participants were categorized as PPV23 responders. Bi-exponential decay models indicated comparable polysaccharide-specific IgG decay rates between responders and non-responders, but longer persistence of IgG concentrations ≥ 1.3 μg/ml among responders. Vaccine responsiveness was consistently associated with higher baseline IgG concentrations and circulating plasmablast numbers. Additional positive associations were observed between PPV23 responsiveness and frequencies of CD56dim natural killer cells and monocytes, kidney function, and diabetes; in contrast, no association was observed with frailty.

CONCLUSION: Together, these findings provide insights into the heterogeneity in PPV23-induced immunity among older adults and underscore the potential for baseline immune profiling to inform tailored pneumococcal vaccination strategies.