Loxoribine |
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Vaxjo ID |
61 |
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Vaccine Adjuvant Name |
Loxoribine |
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Alternative Names |
7-allyl-8-oxoguanosine |
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Adjuvant VO ID |
VO_0001300
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Description |
Loxoribine is a guanosine analog derivatized at position N7 and C8. This nucleoside is a very powerful stimulator of the immune system but until recently the mechanisms responsible for this immunostimulatory activity was unknown. It appears that similarly to imiquimod, a small synthetic antiviral molecule, loxoribine activates the innate immune system through Toll-like receptor 7 and that this activation requires endosomal maturation. Loxoribine recognition is restricted to TLR7 (Website 1). |
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Stage of Development |
Clinical Trial |
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Components |
7-allyl-8-oxoguanosine (Vogel and Powell, 1995). |
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Molecular Weight |
339 |
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Appearance |
White, odorless crystalline powder (Vogel and Powell, 1995). |
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Storage |
Store solid under low humidity at -20° C. Stable in solution for at least 4 weeks; found to be very stable at pH 8-11(Vogel and Powell, 1995). |
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Preparation |
Preparation of sterile stock solution (10 mM): Stimulation of TLR7 can be achieved with Loxoribine at a concentration of 1 mM. Resuspend loxoribine in 1.47 ml DMSO to obtain a 100 mM solution. Transfer into a sterile vial.-Add 13.23 ml of endotoxin-free water (Website 1). |
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Dosage |
Typical dose in mice: 1-3 mg/25 g mouse. In humans: 10 mg/kg has been used safely (Vogel and Powell, 1995). |
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Function |
Augmentation of CTL-mediated, NK cell-mediated, macrophage mediated, and LAK cell-mediated cytotoxicity. Inducer of cytokines: IFN(a/b/g, TNFa, TNFb, IL-1a, IL-6. Up regulates humoral immune responses in immunodeficiency. Acts as a surrogate Th signal (Vogel and Powell, 1995). |
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Safety |
Phase I clinical trial complete, without toxicity greater than grade I. No reported toxicity in a lower dose, phase I/II clinical trial. Main side effects noted resemble those of interferon and are transient (Vogel and Powell, 1995). |
| Related Vaccine(s) |
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| References |
Vogel and Powell, 1995: Vogel FR, Powell MF. A compendium of vaccine adjuvants and excipients. Pharmaceutical biotechnology. 1995; 6; 141-228. [PubMed: 7551218].
Website 1: Loxoribine [http://www.invivogen.com/PDF/Loxoribine_TDS.pdf]
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