B- and T-cell immune responses to pneumococcal conjugate vaccines: divergence between carrier- and...

Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material(197) (CRM(197)) produce a strong anti-PnPS antibody response; however, when mice are immunized with 23F PnPS conjugated to CRM(197), they fail to produce a significant anti-PnPS response. In order to determine whether this difference was related to alterations in antigen processing of the carrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM(197) alone or conjugated to 6B, 19F, or 23F PnPS. T-cell proliferative responses to synthetic peptides demonstrated that lymph node cells elicited by the poorly immunogenic conjugate 23F-CRM(197) recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM(197) as well as additional epitopes. Despite marked differences in PnPS-specific immunogenicity, all mice made high titers of CRM(197) antibodies of the immunoglobulin G(1) isotype. Cells from mice immunized with any of the conjugates yielded vigorous T-cell responses to whole antigen. We conclude that the serotype of PnPS can alter the peptide specificities of T-cell responses, but even a poorly immunogenic PnPS conjugate can elicit a significant T-cell response. Thus, conjugation of PnPS to a carrier protein that elicits carrier-specific T- and B-cell responses does not necessarily enhance PnPS immunogenicity.