| Project/Area Number |
07557336
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Immunology
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| Research Institution | HOKKIDO UNIVERSITY |
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Principal Investigator |
AZUMA Ichiro Hokkaido University, Institute of Immunological Science, Professor, 免疫科学研究所, 教授 (50028411)
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| Co-Investigator(Kenkyū-buntansha) |
OHKUMA Kunio The Chemo-Sero-Therapeutic Research Institute, Deputy General Manager, 製造課長
TAKAHASHI Michiaki The Research Foundation for Microbial Diseases of Osaka University, Director, 微生物病研究会, 常務理事 (50029758)
YOO Yung Choon Hokkaido University, Institute of Immunological Science, Lecturer, 免疫科学研究所, 講師 (00261355)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Immunoadjuvant / BCG-cell-wall / Glycolipid (TDM) / MDP derivatives / Recombinant human hepatitis B virus vaccine (rhHBsAg) / ウイルス感染 / 経口免疫 / ロタウイルス / センダイウイルス |
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| Research Abstract |
In this study, we demonstrated that a lipophilic derivative of muramyl dipeptide [MDP-Lys (L18)], two bacterial cell-derived substances, Bacillus Calmette-Gu e rin cell wall skeleton (BCG-CWS) and trehalose-6,6-dimycolate (TDM) augmented antibody response to recombinant human hepatitis B surface antigen (rhHBsAg) when it was co-immunized with rhHBsAg solubilized in PBS.In an anial model that mice were immunized subcutaneously (s.c.) with rhHBsAg (Vac., 25 mug/mouse) admixed with 100 mug/mouse of MDP-Lys (L18), BCG-CWS (Vac/BCG-CWS) or 50 mug/mouse of TDA (Vac/TDM) in o/w emulsion formulatoin, both mice immunized with Vac/BCG-CWS and Vac/TDM showed higher antibody titers to HB antigen (Vac.) than those of mice immunized with the recombinant vaccine alone. The activity of BCG-CWS and TDM to enhance antibody induction seemed to be almost the same with that of MDP-Lys (L18). Furthermore, the enhanced antibody response raised by these compounds was shown to be due to high titers of HB antigen-specific IgG1. In addition, the activity of these three adjuvants to enhance antibody response was show to be higher than that of the present clinical vaccine, aluminium hydroxide-attached rhHBsAg (rhHBsAg-alum). In an analysis of delayd-type hypersensitivity (DTH) reaction that mice were immunized with rhHBsAg admixed with or without each compound in o/w emulsion and followed by intrafootpad (i.f.) injection of rhHBsAg 4 weeks after immunization, mice immunized with Vac/BCG-CWS and Vac/TDN as well as Vac/MDP-Lys (L18) showed a significant increment of swelling reaction. These results suggest that BCG-CWS,TDM and MDP-Lys (L18) are potent adjuvants to enhance immunogenicity of rhHBsAg to induce humoral and cellular response. It was also shown that another MDP derivative, B30-MDP,enhanced cellular and inoculating antibody response to Hantavirus vaccine (B1) in mice.
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