‘Research and Development of Innovative Next-Generation Mucosal Vaccines’

Director/Professor Hiroshi Kiyono

Hiroshi Kiyono

The development of antibiotics and vaccines and the advancement of public health care systems have provided means to prevent and contain infectious diseases, thus contributing to the welfare of humanity and social progress in the 20th century. However, we are now facing new challenges including: 1) The emergence of an entirely new range of problems including drug tolerance, immunocompromised hosts, and hospital acquired infections; 2) Serious problems in developing countries that repeat a vicious cycle of poverty and the spread of infectious diseases; and 3) The occurrence of emerging/reemerging infectious diseases such as AIDS, tuberculosis, and malaria. In advanced countries, the main serious problems include allergic diseases, such as hay fever and food allergy, and cancer. After infection, allergies and cancer often occur in mucosal tissues, such as the respiratory organs, digestive organs, and urogenital organs. Both basic research to clarify the role of the mucosal immune system from a physiological state to pathogenesis, and the development of fundamental technology to modulate immunity artificially, are essential for the production of new preventative treatments and therapies.

In these circumstances, it is important to take the initiative in the development of ‘mucosal vaccines’ as a next-generation strategy for the prevention and medical treatment of illness in our country, which has taken the lead in the promotion of immunological research. These factors are important contributions to international society. In 2011, The Institute of Medical Science at The University of Tokyo (IMSUT) set up an International Research and Development Center for Mucosal Vaccine, to promote cooperation between international researchers in integrating accumulated intellectual technology including immunology, microbiology, oncology, and genome medical science in a cross-disciplinary manner. The center will develop an innovative academic field, termed ‘Mucosal Vaccinology’, by promoting basic research for the medical application of mucosal vaccines with the aim of forming an international hub to foster next generation researchers.

The Division of Mucosal Immunology (Hiroshi Kiyono, Director/Professor) will perform immunodevelopmental studies focusing on M cells, which uptake luminal antigens in the intestine, mechanistic studies of how mucosal-associated lymphoid tissues such as nasopharynx-associated lymphoid tissue (NALT) and tear duct-associated lymphoid tissue (TALT) are formed, and investigations related to host-commensal bacteria interactions. Recently, research into and development of rice-based oral vaccines (MucoRice), generated by the interdisciplinary fusion of medicine, agronomy and engineering, have been developed and human trials of MucoRice Cholera Toxin B subunit (CTB) vaccine, in which CTB is used as an antigen, have been started. The Division of Mucosal Barriology (Koji Hase, Project Professor) explores antigen uptake receptors on specialized epithelial M cells to identify potential targets for mucosal vaccine delivery. Thus, this division aims to develop novel mucosal vaccines by taking advantage of the conjugation of M-cell-receptor ligands with various vaccine antigens. The Division of Innate Immune Regulation (Satoshi Uematsu, Project Professor) is concentrating on the development of innovative mucosal vaccines targeting vitamin A-producing dendritic cells (DCs) in intestinal lamina propria to induce secretory neutralizing IgA antibodies. In addition, the development of new adjuvants that can convert conventional DCs to mucosal DCs with the ability to induce IgA+ plasma cells will be an important focus.

Pharmaceutical companies and vaccine producers will be attracted to the center, as endowed chairs or research collaboration units in order to promote technical cooperation of drug delivery systems, high throughput screening for vaccine target molecules, and infrastructure development for drug product formulations. Furthermore, as a credible exit strategy, we will identify promising applied studies from basic research and unite them with participant companies during the early stages of research, to promote effective practical research and achieve the mission of the center. The center will create state-of-the-art fundamental technology for mucosal vaccine development through industry-university cooperation. Clinical trials, studies and the application of basic research and formulated vaccines will be conducted at the Research Hospital, IMSUT. The center will develop organically from the realization of industry-university cooperation to actual clinical trials performed by IMSUT, with the aim of developing next-generation mucosal vaccines.