B- and T-cell immune responses to pneumococcal conjugate vaccines: Divergence between carrier- and polysaccharide-specific immunogenicity

Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to c arrier protein enhances the magnitude of the polysaccharide-specific antibo dy response, presumably by eliciting T-cell help. However, variability in P nPS serotype-specific immunogenicity has been observed. CBA/J mice immunize d with either 6B or 19F PnPS conjugated to the protein carrier Cross Reacti ve Material(197) (CRM197) produce a strong anti-PnPS antibody response; how ever, when mice are immunized with 23F PnPS conjugated to CRM197, 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 ca rrier protein and the subsequent T-cell responses, we studied proliferation of lymphocytes from CBA/J mice immunized with CRM197 alone or conjugated t o 6B, 19F, or 23F PnPS, T-cell proliferative responses to synthetic peptide s demonstrated that lymph node cells elicited by the poorly immunogenic con jugate 23F-CRM197 recognized many, but not all, of the epitopes recognized by lymph node cells elicited by 6B- and 19F-CRM197 as well as additional ep itopes, Despite marked differences in PnPS-specific immunogenicity, all mic e made high titers of CRM197 antibodies of the immunoglobulin G(1) isotype, Cells from mice immunized with any of the conjugates yielded vigorous T-ce ll responses to whole antigen. We conclude that the serotype of PnPS can al ter the peptide specificities of T-cell responses, but even a poorly immuno genic PnPS conjugate can elicit a significant T-cell response, Thus, conjug ation of PnPS to a carrier protein that elicits carrier-specific T- and B-c ell responses does not necessarily enhance PnPS immunogenicity.