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Imidazoquinoline compound -TLR7/8 agonist
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TLR7/8 agonist - Imidazoquinoline compound | Th1 response
The imidazoquinoline compound R848 (Resiquimod)is a guanosine derivative and an agonist for TLR7 and TLR8.
R848, originally developed as a type I IFN inducer, is an effective adjuvant by activating dendritic cells (DCs) and B cells to induce cytokines optimal for Th1 cell immunity and antibody production.
Unlike other commercially available R848 preparations, InvivoGen's R848 VacciGrade™ is water-soluble and controlled for TLR7/8 potency and TLR4/TLR2 contamination
R848 VacciGrade™ is a high-quality pre-clinical grade.
R848 VacciGrade™ is for research use only, and not for human or veterinary use.
Description: TLR7/8 agonist VacciGrade™
Polarization of adaptive immune response: Th1 response
CAS number: 144875-48-9 (free base)
Working concentration: 10 - 100 μg/mouse
Solubility: 1 mg/ml in physiological water
- Sterility guaranteed
- The absence of bacterial contamination (lipoproteins & endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells
- Endotoxin level < 1 EU/mg (measurement by kinetic chromogenic LAL assay)
R848 VacciGrade™ is provided lyophilized:
- 5 mg of sterile lyophilized R848 VacciGrade™.
- 10 ml sterile endotoxin-free physiological water (NaCl 0.9%).
R848 VacciGrade™ is shipped at room temperature
R848 VacciGrade™ should be stored at 4°C or -20°C.
Lyophilized product is stable 1 year when properly stored.
Upon resuspension, prepare aliquots of R848 VacciGrade™ and store at -20°C for long term storage.
Resuspended product is stable 6 months when properly stored.
Avoid repeated freeze-thaw cycles.Back to the top
VacciGrade™ is a high-quality pre-clinical grade. VacciGrade™ products are filter-sterilized (0.2 µm) and filled under strict aseptic conditions in a clean room*. The absence of bacterial contamination is assessed by a sterility test using a pharmacopeia-derived assay. The level of bacterial contaminants (endotoxins and lipoproteins) in each lot is verified using a LAL assay and/or a TLR2 and TLR4 reporter assay.
*Except for LPS VacciGrade™, which is prepared in a laminar flow hood dedicated to LPS.
R848 (resiquimod), a small molecular weight imidazoquinoline compound, is an immune response modifier with potent antiviral and antitumor activities .
R848 is being evaluated as an adjuvant in FDA-approved clinical vaccine trials. R848 immune properties result from its ability to induce the production of pro-inflammatory cytokines through the activation of Toll-like receptor (TLR)-7 and TLR8 .
In vitro and in vivo studies have shown that R848 promotes the secretion of Th1 cytokines, including IFN-γ, IFN-α, IL-12 and TNF-α [3-7].
R848 is capable of skewing antibody responses toward a Th1 IgG2a response and away from a Th2 IgE response, a feature mediated in part by IFN-α and IL-12.
Unlike most adjuvants, R848 can be administered by a different route than the antigen, suggesting that it does not produce a depot effect.
Preclinical studies in mice have shown that R848 is able to promote adaptive immune responses to codelivered antigens and provide protection against live infection challenges [4, 6, 8, 9].
1. Stanley MA., 2002. Imiquimod and the imidazoquinolines: mechanism of action and therapeutic potential. Clin Dermatol 27:571–7.
2. Hemmi H. et al., 2002. Small anti-viralcompounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3:196-200.
3. Wagner tL. et al., 1999. Modulation of TH1 and TH2 cytokine production with the immune response modifiers, R-848 and imiquimod. Cell. Immunol. 191, 10, 1999.
4. Vasilakos Jp. et al., 2000. Adjuvant activities of immune response modifier R-848: comparison with CpG ODN. Cell. Immunol. 204:64-74.
5.Thomsen L. et al., 2004. Imiquimod and resiquimod in a mouse model: adjuvants for DNA vaccination by particle-mediated immunotherapeutic delivery. Vaccine 22:1799-1809.
6. Baldwin sL. et al., 2009. Intradermal immunization improves protective efficacy of a novel TB vaccine candidate. Vaccine 27:3063-3071.
7. Ma Y. et al., 2010. Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue engineered immunological model. Immunology 130:374-387.
8. tomai MA. et al., 2000. The immune response modifiers imiquimod and R-848 are potent activators of B lymphocytes. Cell. Immunol. 203:55-65.
9. Zhang WW. & G. Matlashewski. 2008.Immunization with a Toll-like receptor 7 and/or 8 agonist vaccine adjuvant increases protective immunity against Leishmania major in BALB/c mice. Infect. Immun. 76:3777-3783.