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

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.

Vasilakos JP ，Smith RM ，Gibson SJ ，Lindh JM ，Pederson LK ，Reiter MJ ，Smith MH ，Tomai MA ... -  《CELLULAR IMMUNOLOGY》

Vaccinations with T-helper type 1 directing adjuvants have different suppressive effects on the development of allergen-induced T-helper type 2 responses.

Trujillo-Vargas CM ，Mayer KD ，Bickert T ，Palmetshofer A ，Grunewald S ，Ramirez-Pineda JR ，Polte T ，Hansen G ，Wohlleben G ，Erb KJ ... -  《CLINICAL AND EXPERIMENTAL ALLERGY》

Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice.

Inoue J ，Yotsumoto S ，Sakamoto T ，Tsuchiya S ，Aramaki Y ... -  《JOURNAL OF CONTROLLED RELEASE》

CpG ODN mediated prevention from ovalbumin-induced anaphylaxis in mouse through B cell pathway.

Xu W ，Tamura T ，Takatsu K 《INTERNATIONAL IMMUNOPHARMACOLOGY》

An ovalbumin-IL-12 fusion protein is more effective than ovalbumin plus free recombinant IL-12 in inducing a T helper cell type 1-dominated immune response and inhibiting antigen-specific IgE production.

Kim TS ，DeKruyff RH ，Rupper R ，Maecker HT ，Levy S ，Umetsu DT ... -  《JOURNAL OF IMMUNOLOGY》