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. 2022 Apr 18;60(5):550–559. doi: 10.1007/s12275-022-1661-7

The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo

Kyungseob Noh 1,2,#, Eun Ju Jeong 1,3,#, Timothy An 1,2, Jin Soo Shin 1, Hyejin Kim 1, Soo Bong Han 1,3,✉, Meehyein Kim 1,2,✉
PMCID: PMC9014970  PMID: 35437625

Abstract

Adjuvants are substances added to vaccines to enhance antigen-specific immune responses or to protect antigens from rapid elimination. As pattern recognition receptors, Toll-like receptors 7 (TLR7) and 8 (TLR8) activate the innate immune system by sensing endosomal single-stranded RNA of RNA viruses. Here, we investigated if a 2,4-diaminoquinazoline-based TLR7/8 agonist, (S)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexan-1-ol (named compound 31), could be used as an adjuvant to enhance the serological and mucosal immunity of an inactivated influenza A virus vaccine. The compound induced the production of proinflammatory cytokines in macrophages. In a dose-response analysis, intranasal administration of 1 µg compound 31 together with an inactivated vaccine (0.5 µg) to mice not only enhanced virus-specific IgG and IgA production but also neutralized influenza A virus with statistical significance. Notably, in a virus-challenge model, the combination of the vaccine and compound 31 alleviated viral infection-mediated loss of body weight and increased survival rates by 40% compared with vaccine only-treated mice. We suggest that compound 31 is a promising lead compound for developing mucosal vaccine adjuvants to protect against respiratory RNA viruses such as influenza viruses and potentially coronaviruses.

Keywords: influenza virus, chemical vaccine adjuvant, TLR7/8 agonist, mucosal immunity, nasal vaccine

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (NRF-2019M3E5D5066827 to S. B. Han) and an intramural grant funded by KRICT (SI2232-20 to M. Kim and S. B. Han).

Conflict of Interest

The authors have no conflict of interest to report.

Footnotes

These authors contributed equally to this work.

Contributor Information

Soo Bong Han, Email: sbhan@krict.re.kr.

Meehyein Kim, Email: mkim@krict.re.kr.

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