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- The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo
- Kyungseob Noh , Eun Ju Jeong , Timothy An , Jin Soo Shin , Hyejin Kim , Soo Bong Han , Meehyein Kim
- J. Microbiol. 2022;60(5):550-559. Published online April 18, 2022
- DOI: https://doi.org/10.1007/s12275-022-1661-7
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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.
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