tetano
Editor, Senior Moderator
J Microbiol
. 2022 Apr 18.
doi: 10.1007/s12275-022-1661-7. Online ahead of print.
The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo
Kyungseob Noh[SUP] #[/SUP][SUP] 1 2 [/SUP], Eun Ju Jeong[SUP] #[/SUP][SUP] 1 3 [/SUP], Timothy An[SUP] 1 2 [/SUP], Jin Soo Shin[SUP] 1 [/SUP], Hyejin Kim[SUP] 1 [/SUP], Soo Bong Han[SUP] 4 5 [/SUP], Meehyein Kim[SUP] 6 7 [/SUP]
Affiliations
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: TLR7/8 agonist; chemical vaccine adjuvant; influenza virus; mucosal immunity; nasal vaccine.
. 2022 Apr 18.
doi: 10.1007/s12275-022-1661-7. Online ahead of print.
The efficacy of a 2,4-diaminoquinazoline compound as an intranasal vaccine adjuvant to protect against influenza A virus infection in vivo
Kyungseob Noh[SUP] #[/SUP][SUP] 1 2 [/SUP], Eun Ju Jeong[SUP] #[/SUP][SUP] 1 3 [/SUP], Timothy An[SUP] 1 2 [/SUP], Jin Soo Shin[SUP] 1 [/SUP], Hyejin Kim[SUP] 1 [/SUP], Soo Bong Han[SUP] 4 5 [/SUP], Meehyein Kim[SUP] 6 7 [/SUP]
Affiliations
- PMID: 35437625
- DOI: 10.1007/s12275-022-1661-7
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: TLR7/8 agonist; chemical vaccine adjuvant; influenza virus; mucosal immunity; nasal vaccine.