Abstract
Pneumococcal vaccination is crucial in preventing Streptococcus pneumoniae infections in older adults. However, vaccine responses often diminish with age. This study investigates serotype-specific IgM and IgG responses in relation to opsonophagocytic activity (OPA) following thirteen-valent pneumococcal conjugate (PCV13) vaccination in younger (26-49 y; n = 44), middle-aged (50-64 y; n = 71), and older adults (65-98 y; n = 141). Both OPA and IgM responses declined with age, while IgG responses remained relatively stable. In younger adults, post-PCV13 OPA correlated moderate-to-strong with IgM for 8/13 serotypes and with IgG for only 4/13 serotypes. In contrast, middle-aged and older adults showed strong correlations between OPA and both IgM (10/13 serotypes) and IgG (12/13 serotypes). Overall, post-PCV13 OPA was predominantly associated with IgM levels. These observations suggest that declines in IgM, rather than IgG responses, explain reduced PCV13-induced opsonophagocytic activity in aging adults and may inform future vaccination strategies to enhance protection of older adults against pneumococcal disease.