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

doi:10.1007/s12275-022-1661-7

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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 ^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; Journal of Microbiology 2022;60(5):550-559.
DOI: https://doi.org/10.1007/s12275-022-1661-7
Published online: April 18, 2022

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 Korea¹Infectious 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

Corresponding author: Soo Bong Han , Tel: +82-42-860-7540;,
Meehyein Kim , Tel: +82-42-860-7540;,

Received: 21 December 2021 • Revised: 24 February 2022 • Accepted: 28 February 2022

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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.

Keywords: amplicon sequencing;kimchi microbial community;metabolomics;microbiota;obesity

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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

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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