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

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.

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 CD56^dim natural killer cells and monocytes, kidney function, and diabetes; in contrast, no association was observed with frailty.

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.