Responses to conjugate vaccines

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Polysaccharides on bacterial cells are often poorly immunogenic but represent an important target for immune protection. One approach to overcoming this problem is to attach the polysac-charide to a carrier protein that elicits a strong T-cell immune response. The Hib conjugate vaccine provides an example of a large carbohydrate molecule that cannot elicit the help of thy-mus-processed T cells by itself. When conjugated to diphtheria toxoid, an aggregated glycoprotein, T-cell help can be obtained.

Figure 20.12 Surface molecules involved in T-dependent B-cell activation in T zones. B cells take up antigen that they bind specifically through their surface Ig. This is internalized, broken down to peptides and the peptides are presented on the B cell surface, held in the peptide-binding grooves of MHC class II molecules (Figure 20.3). Cross-linking of surface Ig by antigen induces the endocytosis of the antigen-antibody complex and signals upregulation of CD40 expression and de novo B7.1 and B7.2 expression. Ifthis B cell interacts with a primed T cell that recognizes the peptide complex with class II MHC molecules, there will be costimulation through the molecule CD28, which is constitutively expressed by CD4 T cells, and this can result in further signalling through co-stimulatory molecules that are transiently expressed on the T cell surface; CD40 ligand exemplifies these transiently expressed signalling molecules. These interactions can lead to B- and T-cell proliferation and differentiation and may also induce cytokine secretion by the cells. Cytokine receptor expression by the B cell and the T cell is initiated or upregulated. The arrows indicate that TCR engagement induces CD40 ligand expression and that engagement of these molecules by their counterstructures on the B cell delivers further signals to the T cell. CD40 ligation induces Ig class switching in the B cell and migration as indicated in Figure 20.11.

After administration, the polysaccharide is bound by B cells with surface immunoglobulin that can recognize it and the conjugate molecule is internalized. The protein is broken down into peptides in the antigen-processing endosome and diphtheria toxin-derived peptides are presented on the cell surface. This

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Figure 20.13 Processing of a conjugate vaccine between diphtheria toxoid (magenta) and the polyribosyl ribose phosphate of the capsule of Haemophilus influenzae B (green). A B cell with specificity for the capsular polysaccharide binds the conjugate vaccine with its surface Ig (black). The complex is endocytosed and the protein components are broken down to peptides (Figure 20.3). Peptides derived from the diphtheria toxoid are subsequently presented on the B-cell surface in association with class II MHC (blue and pink).

enables a Hib-specific B cell to obtain T-cell help from a diphtheria toxoid-specific T cell (Figure 20.13).

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