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Adjuvant activities of immune response modifier R-848: comparison with CpG ODN
J P Vasilakos1, R M Smith, S J Gibson
1Department of Pharmacology, 3M Pharmaceuticals, St. Paul, Minnesota 55144, USA.
Cellular Immunology
|September 28, 2000
Summary
R-848 and imiquimod, immune modifiers, enhance Th1 antibody responses (IgG2a) and suppress Th2 responses (IgE). These compounds show potential as vaccine adjuvants by inducing key cytokines and boosting acquired immunity.
Area of Science:
- Immunology
- Vaccinology
- Pharmacology
Background:
- R-848 and imiquimod are immune response modifiers that induce cytokines like IFN-alpha, TNF-alpha, IL-12, and IFN-gamma.
- These cytokines significantly influence the acquired immune response.
Purpose of the Study:
- To investigate the effects of R-848 on acquired immunity, including immunoglobulin secretion and cytokine production.
- To compare the immune-modulating effects of R-848 with Th1 CpG ODN.
Main Methods:
- Evaluation of immunoglobulin secretion (IgG2a, IgE) and Ag-specific T cell cytokine production.
- In vivo cytokine profiling following administration of R-848 and CpG ODN.
- Comparison of subcutaneous and oral administration routes for R-848 and imiquimod.
Main Results:
- R-848 and CpG ODN promote Th1 (IgG2a) and suppress Th2 (IgE) antibody responses, with or without alum adjuvant.
- Both compounds can initiate an immune response by enhancing IgG2a levels independently.
- R-848 and imiquimod are active via subcutaneous and oral routes; R-848's adjuvant activity is linked to specific cytokine induction.
Conclusions:
- R-848 and imiquimod demonstrate potent adjuvant properties, enhancing Th1 immunity and potentially serving as vaccine adjuvants.
- These imidazoquinolines may be valuable in therapeutic strategies targeting Th2-mediated pathological conditions.