BBIQ, a pure TLR7 agonist, is an effective influenza vaccine adjuvant
Deepender Kaushik, Simran Dhingra, Madhuri T. Patil, Sakshi Piplani, Varun Khanna, Yoshikazu Honda‐Okubo, Lei Li, Johnson Fung, Isaac G. Sakala, Deepak B. Salunke, Nikolai Petrovsky
Abstract
molecular modeling studies predicted that BBIQ had a higher TLR7 docking score and binding free energy than imiquimod, the gold standard TLR7 agonist. To circumvent the availability issue, we developed an improved and higher yield method to synthesize BBIQ. Testing BBIQ on human and mouse TLR7 reporter cell lines confirmed it to be TLR7 specific with significantly higher potency than imiquimod. To test its adjuvant potential, BBIQ or imiquimod were admixed with recombinant influenza hemagglutinin protein and administered to mice as two intramuscular immunizations 2 weeks apart. Serum anti-influenza IgG responses assessed by ELISA 2 weeks after the second immunization confirmed that the mice that received vaccine admixed with BBIQ had significantly higher anti-influenza IgG1 and IgG2c responses than mice immunized with antigen alone or admixed with imiquimod. This confirmed BBIQ to be a TLR7-specific adjuvant able to enhance humoral immune responses.