Project/Area Number |
11670844
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
|
Research Institution | Leprosy Research Center, National Institute of Infectious Diseases (2000) Yokohama City University (1999) |
Principal Investigator |
ISHII Norihisa National Institute of Infectious Diseases, Department of Bioregulation, Leprosy Research Center, Director, ハンセン病研究センター・生体防御部, 部長 (50159670)
|
Co-Investigator(Kenkyū-buntansha) |
SUGITA Yasuyuki Yokohama City University School of Medicine, Department of Dermatology, Assistant Professor, 医学部, 講師 (30264617)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | DNA vaccine / HIV / Leprosy / plasmid DNA / stripping / topical application / 感染防御 |
Research Abstract |
Topical application of DNA vaccine to the skin is more useful against infections. To find a less expensive and less cumbersome vaccination method, we administered the HIV-1 DNA vaccine to the skin of mice by improved topical application with elimination of keratinocytes using fast acting adhesive. Our results revealed that HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. A high level of HIV-1-specific cytotoxic T lymphocyte (CTL) response was observed and the cytokine assays revealed that improved skin painting of DNA vaccine induces a high level of IFN-_and IL-4 production, when immune spleen cells were cocultured with HIV-1 antigen. Coadministration of the DNA vaccine with IL-12 expression plasmids and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmids induced high levels of both HIV-specific CTL and delayed type hypersensitivity (DTH) by topical application. These immune responses were well inhibited by intradermal injection of anti-CD11c or anti-I-A/I-E antibody. These results suggest that topical administration of DNA vaccine is an efficient route and the immune response may be induced by DNA plasmids taken by dendritic cells or Langerhans cells. Finally, topical application to the skin may be very useful for the prevention of infectious diseases.
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