Laboratory of Immune Modulation

1. Members

• Project Leader – Taku Kouro
• Researcher – Junichi Dohkan
• Project Research Scientist – Kaori Shinoda

2. Background and Objectives

Development of innovative or more effective vaccines is social requirement as defenses to emerging- and re-emerging infectious diseases. For development of good vaccines, it is important not only to select best epitopes but also to find means to induce immune response effectively in appropriate fashion. Although compounds with such property, namely immune adjuvant, are already in use, much more effective and function-oriented adjuvant is needed.

There are many kinds of immune cells working as a complex network. To find target for function-oriented adjuvant, we need to understand roles and mechanisms of each immune cells. Thus we are focusing on two points as below.

1) Revealing regulatory mechanisms of immune system in cellular- and molecular levels.
2) Developing effective screening systems for compounds that modulate immune response using advanced tissue culture technologies.

3. Research Overview

(1) Development of “Natural antibody-boosting adjuvant” through investigation of functional aspects of natural antibody.

Natural antibodies are immunoglobulin existing prior to infection. With their broad cross-reactivity to various pathogens, natural antibodies are considered to be first line of defense to first time infection. Furthermore, recent reports show that natural antibodies has certain roles in the establishment of acquired immune response, such as production of antigen-specific antibodies and induction of cytotoxic T cells (CTL). Natural antibodies are suggested to have much broader function like clearance of oxidated-LDL which cause atherosclerosis.

Thus, we are aimed to reveal exact role(s) of natural antibodies in immune response. Now we are immunizing natural antibody-deficient mice or mice administrated with natural antibody with model antigens and vaccines in various ways to find out immune response in which natural antibody plays critical role. If we could find such immune response, natural antibody will be a target for novel vaccine adjuvant.

In parallel with it, we are seeking for compound or factor that induce production of natural antibody. Since natural antibodies are produced by B-1 cells, a subset of B lymphocytes, we are developing tissue culture system which enable cultivation of B-1 cells. In such culture system, we will be able to screen compounds that directly induce antibody secretion from B-1 cells. Positive compounds are going to be tested as vaccine adjuvant in vivo.

(2) Establishment of evaluation system for the function and side effect of vaccine adjuvant.

Many adjuvants work with unknown mechanisms because they are found by chance and experience. On the other hand, developing knowledge of innate immune system made it possible to elucidate working mechanism of some adjuvants or even to design adjuvant from its working mechanism. Then we are going to establish assay system that can estimate functional property of adjuvant candidate by patterning action on various immune cells. The system may include cytokine production from macrophages, gene expression in dendritic cells or antibody production from B lymphocytes. Such assay system may be useful for collecting safety data for unwanted effects such as induction of allergy or autoimmunity.

To inquire about the Laboratory of Immune Modulation,please contact

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