Correlation of opsonophagocytosis and passive protection assays using human anticapsular antibodies in an infant mouse model of bacteremia for Streptococcus pneumoniae

An infant mouse assay system for assessment of protective concentrations of human serum pneumococcal anticapsular antibodies is described. Passive imm unization of anticapsular antibodies was evaluated for protection of infant mice challenged with Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 18C, and 23A, with bacteremia as an end point. Protection was defined as no dete ctable bacteremia in 70% of mice 48 h after challenge. Type-specific antica psular concentrations required for protection varied with serotype (less th an or equal to 0.05 to >0.4 mu g/mL). Across serotypes, there was no signif icant correlation between human IgG concentration in mouse serum and protec tion from bacteremia or between IgG concentration and opsonophagocytic tite r. Significant correlation (r = .84, P<.001) was observed between opsonopha gocytic titer of human IgG antibody in mouse sera and protection from bacte remia. Thus, protective concentrations of anticapsular antibodies against b acteremia are serotype dependent. Opsonophagocytosis is a better predictor of in vivo protective capacity of pneumococcal anticapsular antibodies than are ELISA IgG antibody concentrations.