| Project/Area Number |
01480184
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
AZUMA Ichiro Hokkaido Univ., Inst. Immunol. Sci. Professor, 免疫科学研究所, 教授 (50028411)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Chiaki Hokkaido Univ., Inst. Immunol. Sci. Associate Professor, 免疫科学研究所, 助教授 (90082172)
YAMANISHI Koichi Osaka Univ., Res. Inst. Micro. Dis. Associate Professor, 微生物病研究所, 助教授 (10029811)
SAIGKI Ikuo Hokkaido Univ., Inst. Immunol. Sci. Instructor, 免疫科学研究所, 助手 (80133776)
TOKURA Seiichi Hokkaido Univ., Faculty of Science Professor, 理学部高分子学科, 教授 (40000806)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥4,200,000 (Direct Cost: ¥4,200,000)
|
|---|
| Keywords | Muramyl dipeptide (MDP) derivatives / Trehalose-dimycolate (TDM) derivatives / B30-MDP / MDP-Lys (L18) / CM-chitin / Immunoadjuvant activity / Hantaan virus vaccine / Tumor vaccine / ムラミルジペプチド(MDP)誘導体 / 免疫アジュバント / トレハロ-ス-マイコレ-ト / ムラミルジペプチド / マクロファ-ジ活性化 / 1-deoxy-glucosamine-mycolate / 癌転移抑制活性 |
|---|
| Research Abstract |
It is well recognized that the development of potent of potent immunadjuvants is essential for the clinical application of recombinant vaccine. The purpose of this study is as follows : (1) development of potent immunoadjuvants ; (2) the potentiation of antigenicity of recombinant Hantaan virus vaccine ; (3) the application of immunoadjuvants for the development of tumor vaccine.
1. Development of new immunoadjuants : We have already examined the adjuvant activities of more than 500 synthetic compounds by using experimental immune systems in mice and guinea pigs. We have found new synthetic compounds, especially muramyldipeptide (MDP) derivatives and trehlose-dimycolate (TDM) derivatives, were effective as immunoadjuvants. Among the MDP derivatives, we have selected three derivatives, B30-MDP, 1-alphaーS-B30-MDP methyl ester and MDP-Lys (L18), as the immunoadjuvants for the potentiation of nonspecific and specifichost-resistance against bacterial viral infections and cancer. We have also
… More
selected TDM derivatives, TDM (alpha, beta), TDM (beta, beta) and GlcNAcM (1-deoxy). It was shown that these TDM derivatives were less toxic than natural TDM [TDM (alpha, alpha)] in mice and were active as immunoajuvants in mouse system.
2. Application of synthetic immunoadjuvants for the potentiation of vaccine : We have examined B30-MDP to the potentiation of immunogenicity of recombinant vaccine of Hantaan virus. We have immunized the mice with recombinant envelope glycoprotein antigen with B30-MDP. The serum antibody titer against Hantaan titer virus surface glycoprotein antigens was higher than that of control group immunized without B30-MDP. Four weeks later, spleen cells of immunized mice were transferred into suckling mice and those mice were challenged with live Hantaan virus. The survival period of group of the mice which were transferred with the spleen cells of mice immunized with B30-MDP and antigenic glycoprotein, was siginificanly longer than of control mice. These results suggest that B30-MDP is effective for the potentiation of serum antibody production and cell-mediated immunity against cell envelope glycoprotein antigen of Hantaan virus in mice. It was shown that B30-MDP was effective as immunoadjuvant for the potentiation of tumor vaccine. Mice (CDF_1) immunized with irradiated L5178Y-ML25 cells with or without B30-MDP were challenged intravenously with live L5718Y-ML25 cells, and then metastasis of tumor into liver and spleen were measured. The results indicated clearly that the immunization of irradiated tumor cells with B30-MDP prevent the tumor metastasis. Less
|
