The Mucosal Immune System for Vaccine Development

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  • Yoshihara Shintaro
    Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, Institute of Medical Science, University of Tokyo, Tokyo, Japan Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Kiyono Hiroshi
    Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, Institute of Medical Science, University of Tokyo, Tokyo, Japan Division of Gastroenterology, Department of Medicine, CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines (CU-UCSD cMAV), University of California, San Diego, CA, USA Division of Mucosal Vaccine, Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

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  • 粘膜免疫システムを応用したワクチン開発

Abstract

<p>Aero-digestive tract is continuously exposed to infinite beneficial and harmful antigens including microbe via the large surface of mucosal epithelium. The mucosal surface is thus equipped with multi-complexed but harmonized biological components including epithelial-mesenchymal cells, mucosal immunocompetent cells and commensal microbiota, which form “Mucosal multi-ecosystem” for handling numerous numbers of foreign antigens.</p><p>For the initiation of antigen-specific immune responses, nasopharyngeal- and gut-associated lymphoid tissues (NALT and GALT, respectively) equipped with the antigen sampling, -processing and -presentation system are immunologically organized inductive sites for the generation of antigen-specific T cells and B cells. During the antigen presentation process, these lymphocytes also acquired mucosal imprinting molecules (e.g., CCR9 and α4β7) for their preferential migration to distant mucosal effector sites for the induction of antigen-specific secretory IgA (SIgA) antibodies. These evidences are the basic foundation for the development of mucosal vaccine. Nasal and oral vaccines thus induce antigen-specific immune responses at mucosal sites including the respiratory, digestive, and reproductive tracts, and simultaneously inducing antigen-specific immunity in the systemic compartment. We have been developing novel nasal vaccination system using cationic cholesteryl group-bearing pullulan (cCHP) nanogels. Vaccine antigens incorporated into cCHP nanogels induced potent antigen-specific mucosal and systemic immune responses without no brain deposition of antigen via olfactory bulb after nasal administration. Thus, cCHP based nanogel is a safe and effective nasal vaccine delivery system. We will present and discuss our progress on our efforts for the development of nasal vaccines against respiratory infectious diseases.</p>

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