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- Pioneering strategies for overcoming bacterial drug resistance (2026)
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- Two years into COVID-19 pandemic: Where are we? (2022)
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Article
- 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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- 6 Crossref
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Abstract
PDF - 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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Citations
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- Synthetic Cathepsin B Sensitive Adjuvant‐Peptide Conjugates to Target Intracellular Toll‐Like Receptors 7 and 8
Marjolein M. E. Isendoorn, Giulia Castello, Nico J. Meeuwenoord, Martijn Verdoes, Jeroen D. C. Codée, Ferry Ossendorp, Dmitri V. Filippov
ChemistryEurope.2026;[Epub] CrossRef - Efflux-Enhanced Imidazoquinolines To Exploit Chemoresistance
Muhammad Haroon, Sharmin Sultana, Seyedeh A. Najibi, Emily T. Wang, Abbey Michaelson, Pranto S. M. Al Muied, Amy E. Nielsen, Rock J. Mancini
ACS Omega.2025; 10(12): 12319. CrossRef - Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants
Morgan Kim, Kyungseob Noh, Pyeongkeun Kim, Jae Ho Kim, Byeong Wook Choi, Ravi Singh, Jun-Ho Choi, Soo Bong Han, Seong Soon Kim, Eun-Young Lee, Myung Ae Bae, Daeho Shin, Meehyein Kim, Jin Hee Ahn
Journal of Medicinal Chemistry.2024; 67(11): 9389. CrossRef - Evaluation of Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2
Hyeon-Min Cha, Uk-Il Kim, Soo Bin Ahn, Myoung Kyu Lee, Haemi Lee, Hyungtae Bang, Yejin Jang, Seong Soon Kim, Myung Ae Bae, Kyungjin Kim, Meehyein Kim
ACS Infectious Diseases.2023; 9(4): 1033. CrossRef - Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice
Sumin Son, Soo Bin Ahn, Geonyeong Kim, Yejin Jang, Chunkyu Ko, Meehyein Kim, Sang Jick Kim
Antiviral Research.2023; 213: 105591. CrossRef - Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry
Hoyeon Jeon, Younghyun Lim, In-Gu Lee, Dong-In Kim, Keun Pil Kim, So-Hee Hong, Jeongkyu Kim, Youn-Sang Jung, Young-Jin Seo
Journal of Microbiology.2022; 60(11): 1113. CrossRef
- Synthetic Cathepsin B Sensitive Adjuvant‐Peptide Conjugates to Target Intracellular Toll‐Like Receptors 7 and 8
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