Cognate Stimulatory B-Cell–T-Cell Interactions Are Critical for T-Cell Help Recruited by Glycoconjugate Vaccines

Abstract

Covalent linkage of a bacterial polysaccharide to an immunogenic protein greatly enhances the carbohydrate's immunogenicity and induces polysaccharide-specific B-cell memory in vivo. These findings have spurred the development of glycoconjugate vaccines for serious bacterial infections. The specific B-cell–T-cell interactions responsible for recruitment of T-cell help by glycoconjugate vaccines are not well defined. We used mice deficient in molecules critical for stimulatory, cognate B-cell–T-cell interactions to study how T cells improve the immunogenicity of a glycoconjugate vaccine against group B streptococcal disease. Isotype switching to immunoglobulin G (IgG) was abrogated in mice deficient in major histocompatibility complex (MHC) class II antigen (Ag)–T-cell receptor (TCR), B7-CD28, or CD40-CD40L interactions. However, expression of either the B7-1 or the B7-2 molecule on antigen-presenting cells was sufficient for optimal T-cell costimulation. T cells activated by the vaccine also played a pivotal role in determining the magnitude of the IgM response to the polysaccharide. Comparable results were obtained with pathway antagonists. These data suggest that MHC class II Ag-TCR, B7-CD28, and CD40-CD40L interactions are critical for immune responses to glycoconjugate vaccines in vivo.

Development of ADA Against Recombinant Human Interferon Beta in Immune Tolerant Mice Requires Rapid Recruitment of CD4+ T Cells, Induces Formation of Germinal Centers but Lacks Susceptibility for (Most) Adjuvants

“…39,44 Moreover, they have been also shown to trigger memory formation, specific to TI counterpart of conjugates. 45,46 However, the rechallenge of tg mice with rhIFN$-1a did not result in enhanced ADA production in contrast to non-tg mice. That strongly suggests that the production of ADA during primary treatment with CTB-rhIFN$ conjugates did not lead to the formation of rhIFN$ specific immunological memory.…”

The advantage of mucosal immunization for polysaccharide‐specific memory responses in early life

“…LT mutants up‐regulate MHC class II, B7 and CD40 on B cells 26. Thus, the effect of LT‐K63 may be mediated by increased T cell help 27, and enhanced interaction of B and T cells via CD28‐B7 and CD40‐CD40L, required for an optimal PS‐specific Ab responses to conjugates 28, associated with increased germinal center formation 29. Neonatal B cells and dendritic cells showed a reduced capacity to present TT and MenC‐PS‐TT conjugate to T cells, which was age‐dependant and reached an adult‐like capacity at 4 weeks of age 30.…”

Activation of Cell‐Mediated Immunity Following Immunization with Pneumococcal Conjugate or Polysaccharide Vaccine*

“…Moreover, conjugate vaccine induces a stronger secondary antibody response than PS vaccine in infants [1, 2, 4]. Although the reasons for the improved effect of conjugate vaccine are not entirely understood, the T lymphocytes activated by the carrier components and the cytokines secreted by them may play an important role in the immune response [8].…”