Cholera toxin B subunit as an immunomodulator for mucosal vaccine delivery

Abstract

This chapter discusses cholera toxin B subunit as an immunomodulator for mucosal vaccine delivery. Efforts to exploit oral immunization for the development of vaccines against the great majority of infections, which directly afflict or invade through the mucosal surfaces, were formerly limited by the modest responses usually generated by the mucosal immune system. In part, this is probably because its functions include the maintenance of homeostasis despite being continuously challenged by large quantities of mainly harmless environmental antigens and commensal microorganisms. In addition, most nonviable immunogens have no affinity for the M cells overlying mucosal inductive sites, such as the intestinal Peyer's patches, and are readily digested within the gut lumen. Thus, oral immunization with conventional nonviable immunogens typically requires the repeated administration of large doses, and yields modest responses that do not persist. However, numerous developments during the past decade have addressed these problems. Notably, the exceptionally potent mucosal immunogenic and adjuvant properties of cholera toxin (CT) and related enterotoxins have been exploited by coupling other antigens to the nontoxic B subunit of CT, or by seeking to detoxify the heat-labile toxin (LT) of Escherichia coli while preserving its adjuvanticity.