Innate signalling molecules as genetic adjuvants do not alter the efficacy of a DNA-based influenza A vaccine.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Storcksdieck Genannt Bonsmann, Michael
MetadataShow full item record
AbstractIn respect to the heterogeneity among influenza A virus strains and the shortcomings of current vaccination programs, there is a huge interest in the development of alternative vaccines that provide a broader and more long-lasting protection. Gene-based approaches are considered as promising candidates for such flu vaccines. In our study, innate signalling molecules from the RIG-I and the NALP3 pathways were evaluated as genetic adjuvants in intramuscular DNA immunizations. Plasmids encoding a constitutive active form of RIG-I (cRIG-I), IPS-1, IL-1β, or IL-18 were co-administered with plasmids encoding the hemagglutinin and nucleoprotein derived from H1N1/Puerto Rico/8/1934 via electroporation in BALB/c mice. Immunogenicity was analysed in detail and efficacy was demonstrated in homologous and heterologous influenza challenge experiments. Although the biological activities of the adjuvants have been confirmed by in vitro reporter assays, their single or combined inclusion in the vaccine did not result in superior vaccine efficacy. With the exception of significantly increased levels of antigen-specific IgG1 after the co-administration of IL-1β, there were only minor alterations concerning the immunogenicity. Since DNA electroporation alone induced substantial inflammation at the injection site, as demonstrated in this study using Mx2-Luc reporter mice, it might override the adjuvants´ contribution to the inflammatory microenvironment and thereby minimizes the influence on the immunogenicity. Taken together, the DNA immunization was protective against subsequent challenge infections but could not be further improved by the genetic adjuvants analysed in this study.
CitationPLoS One. 2020;15(4):e0231138. Published 2020 Apr 3. doi:10.1371/journal.pone.0231138
AffiliationHZI, Helmholtz Zentrum für Infektionsforschung, GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Adjuvant use of the NKT cell agonist alpha-galactosylceramide leads to enhancement of M2-based DNA vaccine immunogenicity and protective immunity against influenza A virus.
- Authors: Fotouhi F, Shaffifar M, Farahmand B, Shirian S, Saeidi M, Tabarraei A, Gorji A, Ghaemi A
- Issue date: 2017 May
- A Bivalent Heterologous DNA Virus-Like-Particle Prime-Boost Vaccine Elicits Broad Protection against both Group 1 and 2 Influenza A Viruses.
- Authors: Jiang W, Wang S, Chen H, Ren H, Huang X, Wang G, Chen Z, Chen L, Chen Z, Zhou P
- Issue date: 2017 May 1
- Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.
- Authors: Chua BY, Wong CY, Mifsud EJ, Edenborough KM, Sekiya T, Tan AC, Mercuri F, Rockman S, Chen W, Turner SJ, Doherty PC, Kelso A, Brown LE, Jackson DC
- Issue date: 2015 Oct 27
- Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice.
- Authors: Goff PH, Hayashi T, He W, Yao S, Cottam HB, Tan GS, Crain B, Krammer F, Messer K, Pu M, Carson DA, Palese P, Corr M
- Issue date: 2017 Oct 1
- Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses.
- Authors: Goff PH, Hayashi T, Martínez-Gil L, Corr M, Crain B, Yao S, Cottam HB, Chan M, Ramos I, Eggink D, Heshmati M, Krammer F, Messer K, Pu M, Fernandez-Sesma A, Palese P, Carson DA
- Issue date: 2015 Mar