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

Research output: Contribution to journalArticlepeer-review

Abstract

Better adjuvants are needed for vaccines against seasonal influenza. TLR7 agonists are potent activators of innate immune responses and thereby may be promising adjuvants. Among the imidazoquinoline compounds, 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ) was reported to be a highly active TLR7 agonist but has remained relatively unexplored because of its commercial unavailability. Indeed, in silico 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.

Original languageEnglish
Pages (from-to)1989-1996
Number of pages8
JournalHuman Vaccines and Immunotherapeutics
Volume16
Issue number8
Early online date16 Apr 2020
DOIs
Publication statusPublished - 2 Aug 2020

Bibliographical note

© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

Keywords

  • adjuvant
  • Imidazoquinoline
  • imiquimod
  • in-silico modeling
  • influenza
  • TLR7
  • TLR8
  • vaccine

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