Age-related decline in IgM responses associate with reduced opsonophagocytic activity following PCV13 vaccination

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.