| Title | The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo |
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| Author | Kyungseob Noh1,2, Eun Ju Jeong1,3, Timothy An1,2, Jin Soo Shin1, Hyejin Kim1, Soo Bong Han1,3*, and Meehyein Kim1,2* |
| Address | 1Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea, 2Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea, 3Medicinal Chemistry and Pharmacology, University of Science and Technology (UST), Daejeon 34113, Republic of Korea |
| Bibliography | Journal of Microbiology, 60(5),550-559, 2022, |
| DOI | 10.1007/s12275-022-1661-7 |
| Key Words | influenza virus, chemical vaccine adjuvant, TLR7/8 agonist, mucosal immunity, nasal vaccine |
| 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-diaminoquinazolinebased 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. |