2004 Fiscal Year Final Research Report Summary
Study about mechanism of action of vaccine therapy and their antiviral potential: development of more potent and new regimen of vaccine therapy
| Project/Area Number |
15590655
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Ehime University |
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Principal Investigator |
ONJI Morikazu Ehime university, School of Medicine, Professor, 医学部, 教授 (10112260)
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| Co-Investigator(Kenkyū-buntansha) |
HIASA Yoichi Ehime University, School of Medicine, Instructor, 医学部附属病院, 助手 (70314961)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Hepatitis B Virus / Vaccine / Dendritic cell |
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| Research Abstract |
Vaccine therapy, in which vaccine containing hepatitis B surface antigen(HBsAg) is administered to hepatitis B virus(HBV) transgenic mouse (HBV-Tg), has shown potent immune modulatory and antiviral potential. Study about the mechanism of action has shown that activation of antigen-presenting dendritic cells(DCs) is related to the therapeutic efficacy of vaccine therapy in HBV-Tg. Accordingly, we postulated that a better therapeutic vaccine can be developed by loading HBsAg on DCs (HBsAg-pulsed DC). HBsAg-pulsed DCs were first prepared by culturing murine spleen DCs with HBsAg for 24-48 hours. Phenotypic analysis revealed that HBsAg-pulsed DCs expressed significantly increased levels of MHC class II and CD86, induced and produced significantly higher levels of proinflammatory cytokines such as inter leukin-12, tumor necrosis factor-alpha and interferon-gamma compared to unpulsed DCs. Administration of HBsAg-pulsed DCs to HBVTg for two times caused negativity of HBsAg in HBV-Tg. HBV-Tg a
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dministered with HBsAg-pulsed DCs also developed antibody to HBsAg (anti-HBs) in the sera. HBsAg-pulsed DCs were equally effective to induce anti-HBs in immunosuppressed HBV-Tg, which was prepared by daily administration of tacrolimus to HBV-Tg.
Inspired by these studies, we decided to prepare HBsAg-pulsed human DCs. Human DCs were enriched from an adherent population of peripheral blood mononuclear cells. Human DCs were cultured with a commercial vaccine containing HBsAg for 6-24 hours to prepare HBsAg-pulsed human DCs. After confirming that HBsAg-pulsed DCs expressed HBsAg in an immunogenic form, we administered HBsAg-pulsed DCs to human volunteers after getting permission from the ethical committee of our university. Administration of HBsAg-pulsed DCs was safe to all volunteers and none of them exhibited any sign of generalized inflammation or abnormal liver and kidney function tests. These volunteers did not develop any autoimmune diseases. Injection of HBsAg-pulsed DCs induced anti-HBs in all volunteers, although the levels of anti-HBs were highly heterogeneous among volunteers. These studies have provided the ethical and scientific basis for using HBsAg-pulsed DCs for treatment of patients with chronic hepatitis B. Less
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Research Products
(15 results)
