Adjuvant activities of immune response modifier R-848: comparison with CpG ODN

Cell Immunol. 2000 Aug 25;204(1):64-74. doi: 10.1006/cimm.2000.1689.


R-848 and imiquimod belong to a class of immune response modifiers that are potent inducers of cytokines, including IFN-alpha, TNF-alpha, IL-12, and IFN-gamma. Many of these cytokines can affect the acquired immune response. This study examines the effects of R-848 on aspects of acquired immunity, including immunoglobulin secretion, in vivo cytokine production, and Ag-specific T cell cytokine production. Results are compared with those of Th1 CpG ODN. R-848 and CpG ODN are effective at skewing immunity in the presence of Alum toward a Th1 Ab response (IgG2a) and away from a Th2 Ab response (IgE). R-848 and CpG ODN are also capable of initiating an immune response in the absence of additional adjuvant by specifically enhancing IgG2a levels. Both R-848 and imiquimod showed activity when given subcutaneously or orally, indicating that the compound mechanism was not through generation of a depot effect. Although CpG ODN behaves similarly to R-848, CpG ODN has a distinct cytokine profile, is more effective than R-848 when given with Alum in the priming dose, and is active only when given by the same route as the Ag. The mechanism of R-848's adjuvant activity is linked to cytokine production, where increases in IgG2a levels are associated with IFN-alpha, TNF-alpha, IL-12, and IFN-gamma induction, and decreases in IgE levels are associated with IFN-alpha and TNF-alpha. Imiquimod also enhances IgG2a production when given with Ag. The above results suggest that the imidazoquinolines R-848 and imiquimod may be attractive compounds for use as vaccine adjuvants and in inhibiting pathological responses mediated by Th2 cytokines.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic*
  • Administration, Oral
  • Animals
  • Cell Separation
  • Cytokines / analysis
  • Female
  • Imidazoles / immunology*
  • Immunization, Secondary
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / immunology*
  • Ovalbumin / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Vaccination


  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cytokines
  • Imidazoles
  • Immunoglobulin G
  • Oligodeoxyribonucleotides
  • Immunoglobulin E
  • Interferon-gamma
  • Ovalbumin
  • resiquimod