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Oral delivery of vaccines results in these being taken up by specialised microfold epithelial cells covering Peyer's patches of the gastrointestinal tract, therefore stimulating regulatory T cells and surface IgA positive (sIgA+) B cells. T helper cells can be divided into 2 subsets, type 1 (T(H)1) and type 2 (T(H)2), according to their function and the cytokines they secrete. T(H)1 cytokines such as interleukin (IL)-2, interferon-gamma and tumour necrosis factor-beta (TNFbeta) elicit activation of T cells and macrophages, whereas T(H)2 cytokines such as IL-4, IL-5, IL-6 and IL-10 favour mucosal and parenteral B cell responses. Therefore, T(H)2-type T cells are of particular interest for mucosal responses, since they help in the differentiation of sIgA+ B cells into IgA-producing plasma cells. As a result, one can take advantage of the fact that different forms of antigen delivery systems generally influence the outcome of an immune response, and use those that best induce mucosal responses. An example of this would be orally administered live attenuated Salmonella versus the oral administration of cholera toxin. The first induces a dominant T(H)1-type response, and the second a T(H)2-type response. Thus these 2 delivery systems can be exploited in order to elicit the desired immune response depending on the protective response required. Alternatively, encapsulating antigens into polyglycolide microspheres or liposomes, or incorporating them into immune-stimulating complexes, has facilitated the delivery of antigens which otherwise do not result in an immune response when given orally. Much progress is being made in the construction of attenuated viral and bacterial vectors for the delivery of antigen to mucosal sites. For example, poliovirus has been used as a vector to deliver both rotavirus and HIV antigens. Bacterial vectors and attenuated mutant bacteria for use in vaccines have also been extensively researched. Examples of these include Salmonella typhi mutants, Vibrio cholerae, Shigella species, Helicobacter pylori and Campylobacter jejuni. In addition, new approaches are being developed to induce responses at mucosal surfaces such as the gastrointestinal, respiratory and genitourinary tracts. These include the use of adjuvants that stimulate mucosal responses such as cholera toxin and Escherichia coli heat labile toxin, as well as the coexpression of cytokine genes with antigenic proteins on live vectors to drive the immune response so that mucosal responses are favoured. Furthermore, nucleic acid vaccines and the potential use of transgenic plants are new technologies that are contributing to our ability to induce responses at mucosal surfaces.
Sabbaj
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Department of Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA.
Kiyono
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McGhee
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