Process Optimization of 1-Benzyl-2-Butyl-1H-imidazo[4,5-C]quinolin-4-Amine, a Pure TLR7 Agonist and its Demonstration as Influenza Vaccine Adjuvant
Posted: 14 Feb 2020
Date Written: February 12, 2020
New adjuvants are required to enhance the immunogenicity of vaccines such as those against seasonal influenza, which are only partially protective at best. TLR7 ligands have been shown to enhance humoral and cellular immunity and are promising new class of vaccine adjuvants. The imidazo[4,5-c]quinoline scaffold with C4 amino functionality and with specific substitution at N1 and C2 position is specifically recognized by TLR7 and/or TLR8. 1-Benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ), remains amongst the most active known pure human TLR7 agonists. However, no in vivo adjuvant studies have been reported on this compound due to the low yields of synthetic processes and hence its commercial unavailability. We reveal here an improved synthetic method for the preparation of BBIQ which enabled its activity to be fully characterized for the first time including as a vaccine adjuvant, in vivo. These studies confirmed that BBIQ is a TLR7 specific agonist with a higher potency than imiquimod and demonstrated for the first time its ability to act as a vaccine adjuvant when formulated with an influenza vaccine.
Keywords: TLR agonists, Vaccine Adjuvant, BBIQ
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