Imiquimod and resiquimod in a mouse model: adjuvants for DNA vaccination by particle-mediated immunotherapeutic delivery
Autor: | Maria G. Daly, Lindy L. Thomsen, Sara Brett, Peter Topley, Tite John Philip |
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Rok vydání: | 2004 |
Předmět: |
CD4-Positive T-Lymphocytes
Ovalbumin Injections Subcutaneous medicine.medical_treatment T cell Imiquimod CD8-Positive T-Lymphocytes Biology DNA vaccination Interferon-gamma Mice chemistry.chemical_compound Immune system Adjuvants Immunologic Vaccines DNA medicine Animals Mice Inbred BALB C General Veterinary General Immunology and Microbiology CD11 Antigens Imidazoles Public Health Environmental and Occupational Health Immunotherapy TLR7 Biolistics Th1 Cells Microspheres Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure chemistry Immunology Aminoquinolines Cytokines Molecular Medicine Immunization Lymph Nodes Resiquimod Adjuvant Plasmids medicine.drug |
Zdroj: | Vaccine. 22:1799-1809 |
ISSN: | 0264-410X |
DOI: | 10.1016/j.vaccine.2003.09.052 |
Popis: | Imiquimod, an immune response modifier and inducer of cytokines in vitro and in vivo, has been shown to have potent antiviral and antitumour activity and to act as an adjuvant for protein vaccination. We have undertaken studies in mice to investigate the potential of imiquimod and resiquimod to adjuvant DNA vaccination. These imidazoquinolines were administered by subcutaneous injection at the vaccination site immediately after particle-mediated immunotherapeutic delivery of plasmid DNA using a gene gun. Imiquimod was found to increase the number and maturation status of dendritic cells in draining lymph nodes, and to enhance antigen-specific CD4(+) and CD8(+) T cell responses, as assessed by analyses of clonal expansion, and the quantity and kinetics of cytokine production from these cells in lymph nodes and spleens collected after vaccination. A more substantial increase in IFN-gamma-producing, compared with IL-4-producing CD4(+) T cells suggested that imiquimod biased the immune response towards a predominance of Th1 cells. The analogue resiquimod was found to be to produce a similar Th1 biased immune response with a 10-fold reduced dose compared with imiquimod. Collectively, these studies suggest that both imiquimod and resiquimod may be suitable adjuvants for therapeutic DNA vaccines requiring induction of potent cytotoxic T cell responses. |
Databáze: | OpenAIRE |
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