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https://doi.org/10.1371/journal.pone.0065964
Title: | The Adjuvant Activity of Alphavirus Replicons Is Enhanced by Incorporating the Microbial Molecule Flagellin into the Replicon | Authors: | Knudsen M.L. Johansson D.X. Kostic L. Nordström E.K.L. Tegerstedt K. Pasetto A. Applequist S.E. Ljungberg K. Sirard J.-C. Liljeström P. |
Keywords: | flagellin immunoglobulin G1 immunoglobulin G2 immunoglobulin G2a immunoglobulin G2c immunological adjuvant interferon toll like receptor 5 unclassified drug Alpha virus animal experiment antibody response article controlled study fliC gene innate immunity mouse nonhuman replicon Salmonella typhimurium signal transduction Th1 cell Th2 cell virus recombinant Adjuvants, Immunologic Alphavirus Animals Antibodies, Viral Antigens, Viral Cell Line Cricetinae Flagellin Gene Expression Immunoglobulin G Interferon Type I Mice Mice, Knockout Replicon Salmonella typhimurium Signal Transduction Toll-Like Receptor 5 Alphavirus Bacteria (microorganisms) Mus Salmonella typhimurium |
Issue Date: | 2013 | Citation: | Knudsen M.L., Johansson D.X., Kostic L., Nordström E.K.L., Tegerstedt K., Pasetto A., Applequist S.E., Ljungberg K., Sirard J.-C., Liljeström P. (2013). The Adjuvant Activity of Alphavirus Replicons Is Enhanced by Incorporating the Microbial Molecule Flagellin into the Replicon. PLoS ONE 8 (6) : e65964. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0065964 | Rights: | Attribution 4.0 International | Abstract: | Ligands of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs) stimulate innate and adaptive immune responses and are considered as potent adjuvants. Combinations of ligands might act in synergy to induce stronger and broader immune responses compared to stand-alone ligands. Alphaviruses stimulate endosomal TLRs 3, 7 and 8 as well as the cytoplasmic PRR MDA-5, resulting in induction of a strong type I interferon (IFN) response. Bacterial flagellin stimulates TLR5 and when delivered intracellularly the cytosolic PRR NLRC4, leading to secretion of proinflammatory cytokines. Both alphaviruses and flagellin have independently been shown to act as adjuvants for antigen-specific antibody responses. Here, we hypothesized that alphavirus and flagellin would act in synergy when combined. We therefore cloned the Salmonella Typhimurium flagellin (FliC) gene into an alphavirus replicon and assessed its adjuvant activity on the antibody response against co-administered antigen. In mice immunized with recombinant alphavirus, antibody responses were greatly enhanced compared to soluble FliC or control alphavirus. Both IgG1 and IgG2a/c responses were increased, indicating an enhancement of both Th1 and Th2 type responses. The adjuvant activity of FliC-expressing alphavirus was diminished but not abolished in the absence of TLR5 or type I IFN signaling, suggesting the contribution of several signaling pathways and some synergistic and redundant activity of its components. Thus, we have created a recombinant adjuvant that stimulates multiple signaling pathways of innate immunity resulting in a strong and broad antibody response. © 2013 Knudsen et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161304 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0065964 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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