Chapter category: Vaccines
Polysaccharide Vaccines
New Vaccine Technologies
Edited by: Ronald W. EllisISBN: 1-58706-050-7
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Chapter authors:
Stephen Freese
The immune response to polysaccharide antigens is qualitatively different from that to protein antigens. Considering only those aspects that bear upon immunity to polysac- charides, the differences may be roughly described as follows. Immune cells take up and digest foreign proteins, and the resulting peptide fragments are presented by MHC II molecules at the cell surface for recognition by T cells. Upon recognition of the bound peptide by a T cell it stimulates the B cell to multiply, to switch to the production of soluble immunoglobulins and causes memory B cells to be produced. Memory B cells are long lived and are able to undergo an additional round of genetic rearrangement resulting in an ability to produce antibodies of higher affinity than those produced initially. Because these responses are dependent upon stimulation by T cells, proteins are "T-dependent antigens". Their salient features are a memory response (i.e., priming), class switching, and affinity maturation.1
In contrast to T-dependent antigens, polysaccharides may be taken up by B cells, but can not be loaded into MHC II molecules and can not recruit T cell help. "T-independent antigens" do not produce a memory response, are largely IgM, and affinity of the antibodies does not increase with time.2
An additional feature of T-independent antigens, which is of primary importance for vaccine development, is the failure of children younger than about 18 months to mount an effective response to polysaccharide antigens. Although polysaccharide vaccines are efficacious in older people, they do not protect young children. It is primarily for this reason that conjugate vaccines were developed.3
Since the pioneering work of Goebel and Avery4 it has been appreciated that covalently linking a saccharide to a protein carrier resulted in an immunogen which combined an antisaccharide response with the memory response characteristic of a protein. Essentially a polysaccharide-specific B cell is stimulated and simultaneously provided with a foreign T-cell epitope to garner the benefits T-cell stimulation.
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