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The intestine is a unique organ which is continuously exposed to various antigens such as food-derived antigens, as well as both commensal and pathogenic bacteria, under physiological conditions. Intestinal epithelial cells constitute both a physical and an immunological barrier system against this vast array of antigens. The α1,2-fucose-conjugated carbohydrate chains expressed on intestinal epithelial cells are physiologically and immunologically important and are regulated by type III innate lymphoid cells (ILC3). IL-22-producing ILC3 induce anti-microbial molecules such as RegIIIγ, contributing to the formation of a safeguard system for homeostasis of commensal flora in the intestinal lumen, containment of Alcaligenes in Peyer's patches, and establishment of a defensive platform against infection by pathogenic bacteria. The other intestinal innate immune cell type, the mast cell, is also a critical player. Mast cells are activated by ATP produced in host cells and commensal flora, predisposing to the development of inflammatory bowel diseases. Furthermore, mucosal mast cells regulate the differentiation of follicular helper T cells through ATP signals and contribute to subsequent IgA affinity maturation and regulating the homeostasis of commensal microflora.

Most pathogens invade body through the mucosal epithelium, which is a primary target to prevent the infectious diseases. Mucosal vaccine has been considered to be an effective strategy to establish immunosurveillance against pathogens by the induction of antigen-specific immune responses at both mucosal and systemic immune compartments. The development of antigen delivery system and mucosal adjuvants are required for the sufficient induction of protective immunity in the development of mucosal vaccine. In this review, we shed light on the recent advances in the development of antigen delivery system using microbial functions for mucosal vaccines.

Mucosal vaccination has several advantages compared with that of injection-type vaccination. Secretory IgA(SIgA) produced at mucosal surface plays a key role for inactivation of toxins and inhibition of pathogen invasion. Although oral or nasal vaccination with attenuated live microorganisms have been shown to be effective in the induction of protective immunity, these types of vaccine have the ability to infect transiently to the host. For the development of safe and effective mucosal vaccine, an obvious strategy is the preparation of inactivated subunit-type mucosal vaccine. Here we introduce our frontier technology for the development of rice-based oral vaccines, as a new generation of mucosal vaccine. Further, we also discuss recent progress in the development of other types of mucosal vaccine and adjuvant.

Mucosal surface performs various vital functions, such as respiration, absorption, excretion, and reproduction. At the same time, the mucosal surface is inevitably and continuously exposed to various kinds of external foreign antigens derived from food materials, and both commensal and pathogenic bacteria. Generally, tolerance is induced to beneficial antigens including food proteins and commensal bacteria, while protective immunity is induced against pathogenic bacteria and viruses to exclude these harmful pathogens from the entering into our body. Allergic disease is caused by the unexpected hyper-responsiveness against the unharmful antigens which induce generally tolerance. To establish new generation of the preventive and therapeutic strategies for the control of the allergic diseases, the molecular and cellular understanding of the induction of allergic responses at the mucosal compartment of aero-digestive tract needs to be accomplished. In this review, we focus on the recent progress in our understanding of how allergic diseases are developed in the respiratory and intestinal mucosae and applicable strategy for the mucosal allergy vaccine development and immunotherapy.

Parenteral vaccines are used commonly against most of infectious diseases. It is noted that these injection type vaccines are meant to induce protective immunity in the systemic compartment but not aimed at use of the benefits of mucosal immunity as a first line of defense against mucosal infectious diseases such as AIDS, SARS and Influenza. In addition, one of major practical obstacles to current vaccination is storage of the vaccine under refrigeration (or cold-chain) in the developing countries. To overcome these concerns, a plant-based vaccine is considered to be an attractive strategy. Currently, we have developed a rice-based oral vaccine that offers significant advantages over available vaccines. In the rice-based vaccine MucoRice, cholera toxin B subunit (CTB) as the vaccine antigen was accumulated in protein bodies as rice seed storage organella. When orally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches (PPs), and inducing toxin-specific serum IgG and mucosal IgA antibodies with neutralizing activity. Further, MuocRice CTB remained stable state and maintained immunogenicity at room temperature for 1.5 years and was protected from pepsin digestion in vitro. Taken together, these findings suggest that MucoRice does not require needle/syringe and cold-chain but induces two layers of immunity in both mucosal and systemic compartments, which is the most effective and highly practical global vaccine to combat emerging and re-emerging infectious diseases.

The mucosal immune system acts as the first line of defense against microbial infection through a dynamic immune network based on innate and acquired mucosal immunity. To prevent infectious diseases, it is pivotal to develop effective mucosal vaccines that can induce both mucosal and systemic immune responses, especially secretory IgA (S-IgA) and plasma IgG, against pathogens. Recent advances in medical and biomolecular engineering technology and progress in cellular and molecular immunology and infectious diseases have made it possible to develop versatile mucosal vaccine systems. In particular, mucosal vaccines have become more attractive due to recent development and adaptation of new types of drug delivery systems not only for the protection of antigens from the harsh conditions of the mucosal environment but also for effective antigen delivery to mucosa-associated lymphoid tissues such as Peyer's patches and nasopharynx-associated lymphoid tissue, the initiation site for the induction of the antigen-specific immune response. In this review, we shed light on the dynamics of the mucosal immune system and recent advances toward the development of prospective mucosal antigen delivery systems for vaccines.

Normal mucosal immunity is regulated in a delicate balance between up- and down-regulatory responses to dietal or bacterial antigens. Recent studies demonstrated that pathogenesis of inflammatory bowel disease could be dysregulation of the balance of mucosal immunity. Recent advances in animal models of inflammatory bowel disease, pathogenic roles of mucosal immunoregulatory T cells, cytokines and intestinal flora are reviewed.

Oral or nasal administration of a single high dose or repeated mucosal delivery of low doses of proteins have been shown to induce systemic unresponsiveness in the presence of mucosal IgA responses. The induction of oral tolerance(or mucosally-induced tolerance) is mediated by T cells involved in the generation of active suppression, clonal anergy or clonal deletion. Studies of T helper(Th) cytokine responses have suggested that Th1- and Th2-type cells are involved in the induction of oral tolerance. Further, gamma delta T cells appear to be an important T cell subset for the regulation of oral tolerance.

In the recent years, mucosal immune system is recognized as the new world in the area of immunology. The host is continuously exposed to the numerous numbers of environmental antigens via the mucosa and the skin. A total surface area of the mucosa is approximately 200 times larger than that of the skin, and the former surface area contains a large numbers of lymphoid cells (> 10(11)). In order to provide an effective defence for the host by vaccine, it is logical to consider the mucosal immune system. According to the new informations obtained by the modern cellular and molecular immunobiological knowledges and approaches, the concept of the mucosal immune system has been rapidly proceeded to apply for the development of mucosal vaccine. In this report, we have reviewed and discussed the recent progress in the characterization of mucosal immune system and the development of mucosal vaccine.