ArticleScientific reports2016
Functional properties of flagellin as a stimulator of innate immunity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 66 citations in OpenAlex.
- Oral yeast-displayed SARS-CoV-2 spike protein vaccine enhanced by trimerization and flagellin peptide.Scientific reports · 2026Article
- HIV Membrane-Proximal External Region Scaffolded Immunogen as Killed Whole-Cell Genome-Reduced Vaccines.Viruses · 2026Article
- Article
- Balancing harm and harmony: Evolutionary dynamics between gut microbiota-derived flagellin and TLR5-mediated host immunity and metabolism.Virulence · 2025Review
- Flagellin as a Versatile Adjuvant Platform: Genetic Fusion Approaches for Next-Generation Vaccines.International journal of molecular sciences · 2025Review
- Therapeutic potential of Bacillus sonorensis PMC204 membrane vesicles against drug-resistant Mycobacterium tuberculosis.Medical microbiology and immunology · 2025Article
- Co-Delivery of Multiple Toll-Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy.Advanced healthcare materials · 2025Article
- Multiple Chaperone DnaK-FliC Flagellin Interactions are Required for Pseudomonas aeruginosa Flagellum Assembly and Indicate a New Function for DnaK.Microbial biotechnology · 2025Article
- A simple cost-effective method for purification ofVeterinary research forum : an international quarterly journal · 2025Article
- De novo design of protein minibinder agonists of TLR3.bioRxiv : the preprint server for biology · 2024Article
- Review
- Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery.Vaccines · 2024Review
- Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope.Scientific reports · 2023Article
- Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity.NPJ vaccines · 2023Article
- The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer.Cancer biology & medicine · 2023Article
- Immunogenic Modification of Ligilactobacillus agilis by Specific Amino Acid Substitution of Flagellin.Applied and environmental microbiology · 2022Article
- Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.Pharmaceutics · 2022Review
- Article
- Enhanced serodiagnosis of melioidosis by indirect ELISA using the chimeric protein rGroEL-FLAG300 as an antigen.BMC infectious diseases · 2022Article
- Emerging Concern for Silver Nanoparticle Resistance inFrontiers in microbiology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the development of a well-defined flagellin-based nanoparticle stimulator and also provide a new mechanism of action model explaining how flagellin-triggered innate immunity has evolved to favor localized rather than potentially debilitating systemic immune stimulation. Cell-free protein synthesis (CFPS) was used to facilitate mutational analysis and precisely orientated display of flagellin on Hepatitis B core (HBc) protein virus-like particles (VLPs). The need for product stability and an understanding of mechanism of action motivated investigations indicating that the D0 domain of flagellin is sensitive to amino acid sequence independent hydrolysis - apparently due to the need for structural flexibility during natural flagellin polymerization. When D0-stabilized flagellin was attached to HBc VLPs with the D0 domain facing outward, flagellin's tendency to polymerize caused the VLPs to precipitate. However, attaching the D0 domain to the VLP surface produced a stable nanoparticle adjuvant. Surprisingly, attaching only 2 flagellins per VLP provided the same 1 pM potency as did VLPs with about 33 attached flagellins suggesting that the TLR5 receptor is highly effective in delivering its intracellular signal. These observations suggest that flagellin's protease sensitivity, tendency to aggregate, and very high affinity for TLR5 receptors limit its systemic distribution to favor localized immune stimulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.