Chapter 6 : The Immunobiology of Polysaccharide and Conjugate Vaccines

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Infections with polysaccharide (PS)-encapsulated extracellular bacteria are a major source of global morbidity and mortality among infants, as well as the elderly and immunosuppressed individuals. An understanding of the immunological basis of glycoconjugate interactions is still emerging but is already helping shape strategies to improve conjugate responses. Genetic factors in humans that are known to influence susceptibility to infection with the pneumococcus may also provide a clue to the key factors associated with the immune response to PS antigens. The covalent linkage of PS antigens to immunogenic proteins capable of recruiting CD4 T-cell help to produce conjugate vaccine, first described in the 1930s, results in the elicitation of protective, high-titer-IgG anti-PS responses and the generation of immunologic memory, as well as immunogenicity in the infant host. Conjugate vaccines used clinically are produced by employing a limited number of carrier proteins (e.g., tetanus toxoid (TT), diphtheria toxin or its genetic mutant form CRM197, the outer membrane protein complex [OMPC] of , and more recently, protein D derived from ). Alum acts to promote immunity, likely by serving as a depot for antigen, thus enhancing uptake by antigen-presenting cells (APCs) for presentation of the protein component to CD4 T cells. Effective intranasal immunization appears to require a strong mucosal adjuvant, of which there are several candidates potentially suitable for human use (e.g., CpGODN, LT, and RhinoVax).

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6
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Figure 1

Interaction between PS antigen and B cells. B cells recognize the antigen via the B-cell receptor, and this interaction is sufficient to trigger clonal expansion of the B cells and antibody production. Antibody responses are dominated by the production of IgM, and no affinity maturation of antibodies or memory-B-cell production occurs. CR2, complement receptor 2.

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6
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Image of Figure 2
Figure 2

Interaction between PS-protein conjugate and B cells. B cells recognize the PS antigen via the B-cell receptor while also taking up the carrier protein, processing it, and presenting it to T cells in the context of MHC-II molecules. The CD4 T cell provides the necessary costimulation for the switching of antibody class, affinity maturation, and the generation of memory B cells. CR2, complement receptor 2; TCR, T-cell receptor. Reprinted from ( ) with permission of the publisher.

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6
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Table 1

New bacterial conjugate vaccines tested in animals

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6
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Table 2

Potential new carrier proteins tested in animals

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6
Generic image for table
Table 3

Adjuvants tested in animals

Citation: Goldblatt D, Assari T, Snapper C. 2008. The Immunobiology of Polysaccharide and Conjugate Vaccines, p 67-82. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch6

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