Type 6 and 19 pneumococcal polysaccharides coupled to erythrocytes elicit pneumococcal cell wall-specific primary IgM responses and capsular polysaccharide-specific secondary IgG responses

Abstract

Previous results have shown that the primary murine antibody responses to vaccine preparations of type 6 (S6; Danish type 6A) or type 19 (S19; Danish type 19F) pneumococcal capsular polysaccharides consist entirely of IgM antipneumococcal cell wall carbohydrate (PnC)-specific antibodies. No capsular polysaccharide-specific IgM antibodies were detectable by plaque-forming cell or enzyme-linked immunosorbent assay techniques. In this report, antibodies specific for S6 and S19 capsular polysaccharides were induced in secondary responses to chicken erythrocyte (CRBC) conjugates of S6 and S19. Essentially all detectable IgG produced in the secondary response was capsular polysaccharide specific and included all subclasses of IgG. In contrast, all detectable IgM produced in the primary response to S6-CRBC and S19-CRBC, and the IgM produced in the secondary response to S6-CRBC was not capsular polysaccharide specific since it reacted with PnC. Thus, there is a major change in the specificity of the primary IgM response compared to the secondary IgG response of mice immunized with S6-CRBC or S19-CRBC. Injection of PnC or any PnC-containing polysaccharide prior to immunization with S6-CRBC or S19-CRBC resulted in suppression of the primary IgM response. In contrast, only the capsular polysaccharide used in the immunizing polysaccharide-erythrocyte conjugate suppressed induction of the capsular polysaccharide-specific secondary IgG response. These results suggest that S6 and S19 capsular polysaccharide-specific IgG-producing memory B cells derive from capsular polysaccharide-specific precursors which do not produce detectable antibody after primary immunization.