Serum IgM Antibodies Contribute to High Levels of Opsonophagocytic Activities in Toddlers Immunized with a Single Dose of the 9-Valent Pneumococcal Conjugate Vaccine

In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG antibody concentrations to pneumococcal cap-sular polysaccharides (PPSs) are usually determined, along with the opsonophagocytic activity (OPA) of antipneumococcal anti-bodies. We aimed to determine the role of both IgG and IgM in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1 month after a single PCV9 dose. The OPA for the same serotypes was measured by multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations andMOPAwere measured to PPS of sero-types 6A, 14, and 19F in sera collected 12 months after vaccination. The detectedMOPA titers were high in comparison to the IgG concentrations 1 month after immunization. The IgM concentrations were higher than IgG concentrations for serotypes 6A and 14 (P< 0.001) and as high as IgG for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations with MOPA (r 0.35 to 0.65) was stronger compared to that of the IgG antibodies (r 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera only slightly decreased the OPA activity against serotype 14. At 12 months after immunization, 50 to 100 % of serum samples still showed detectable MOPA activity against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to OPA 1month after a single PCV9 vaccination in toddlers and that functionally active IgM and IgG antibodies per-sist for at least a year. Streptococcus pneumoniae (pneumococcus) is a leading cause ofmorbidity and mortality worldwide. The dramatic succes