Lactic acid bacteria (LAB) are promising mucosal vaccine vectors due to their safety, immunostimulatory properties, and the availability of genetic tools for certain strains. Bacterial flagellin has attracted attention as both a versatile scaffold for antigen surface display and a potent adjuvant via Toll-like receptor 5 (TLR5) activation. Despite these advantages, LAB-derived flagellin remains largely unexplored as an antigen display platform. In this study, we demonstrate the potential of flagellin (FliC2) from Ligilactobacillus agilis , one of the few flagellated LAB species, as a scaffold for the surface display of the HIV-1 membrane-proximal external region (MPER) epitope. Recombinant L. agilis strains were engineered to express FliC2 with the MPER epitope inserted at various positions within its hypervariable domain, identifying optimal sites for effective surface display. To enhance the adjuvant activity of FliC2, specific amino acid substitutions were introduced into the TLR5 recognition site, resulting in improved TLR5-stimulating activity in vitro . Immunization of mice with MPER-displaying L. agilis strains induced MPER-specific IgA and IgG responses, demonstrating the efficacy of the L. agilis flagellin-based display platform in eliciting both mucosal and systemic immune responses. This study is the first to demonstrate LAB-derived flagellin as an antigen display scaffold, highlighting L. agilis flagellin as a promising platform for mucosal vaccine development.

IMPORTANCE:

Lactic acid bacteria (LAB) are promising delivery vehicles of active molecules, and surface display systems are gaining interest for efficiently displaying heterologous peptides and proteins. Flagellin, a TLR5 agonist, has been widely used as an adjuvant and an antigen scaffold, making it a potentially valuable platform for such systems. However, the potential of LAB-derived flagellin as a surface display scaffold remains largely unexplored. This study demonstrates that flagellin from Ligilactobacillus agilis , a flagellated LAB species, effectively functions as an antigen display platform, eliciting mucosal and systemic immune responses. Our findings highlight the feasibility of LAB-derived flagellin as a versatile tool for surface display of heterologous peptides, expanding its potential applications in vaccine development and mucosal immunotherapy.

2024-08-01·Chinese Clinical Oncology

AB020. Flagellin synergistically enhances anti-tumor effect of EGFRvIII peptide in a glioblastoma-bearing mouse brain tumor model

Article

作者: Choi, Jin-Myung ; Jung, Shin ; Liu, Zhi-Peng ; Lim, Sa-Hoe

BACKGROUND:

Glioblastoma (GBM) is the most aggressive type of brain tumor with heterogeneity and strong invasive ability. Treatment of GBM has not improved significantly despite the progress of immunotherapy and classical therapy. Epidermal growth factor receptor variant III (EGFRvIII), one of GBM-associated mutants, is regarded as an ideal therapeutic target in EGFRvIII-expressed GBM patients because it is a tumor-specific receptor expressed only in tumors. Flagellin B (FlaB) originated from Vibrio vulnificus, is known as a strong adjuvant that enhances innate and adaptive immunity in various vaccine models. This study investigated whether FlaB synergistically could enhance the anti-tumor effect of EGFRvIII peptide (PEGFRvIII).

METHODS:

EGFRvIII-GL261/Fluc cells were used for GBM-bearing mouse brain model. Cell-bearing mice were inoculated with phosphate-buffered saline (PBS), FlaB alone, PEGFRvIII alone, and PEGFRvIII plus FlaB. Tumor growth based on magnetic resonance imaging (MRI) and the survival rate was investigated. T cell population was examined by flow cytometry analysis. Both cleaved caspase-3 and CD8+ lymphocytes were shown by immunohistochemistry (IHC) staining.

RESULTS:

The PEGFRvIII plus FlaB group showed delayed tumor growth and increased survival rate when compared to other treatment groups. As evidence of apoptosis, cleaved caspase-3 expression and DNA disruption were more increased in the PEGFRvIII plus FlaB group than in other groups. In addition, the PEGFRvIII plus FlaB group showed more increased CD8+ T cells and decreased Treg cells than other treatment groups in the brain.

CONCLUSIONS:

FlaB can enhance the anti-tumor effect of PEGFRvIII by increasing CD8+ T cell response in a mouse brain GBM model.

2024-05-02·Antimicrobial agents and chemotherapy

Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa

Article

作者: Briard, Benoit ; Fouquenet, Delphine ; Cezard, Adeline ; Sirard, Jean-Claude ; Hervé, Virginie ; Si-Tahar, Mustapha ; Maia, Ana Raquel ; Vasseur, Virginie

ABSTRACT:

The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa (PA) is a significant concern for chronic respiratory disease exacerbations. Host-directed drugs, such as flagellin, an agonist of toll-like receptor 5 (TLR5), have emerged as a promising solution. In this study, we evaluated the prophylactic intranasal administration of flagellin against a multidrug-resistant strain of PA (PA MDR ) in mice and assessed the possible synergy with the antibiotic gentamicin (GNT). The results indicated that flagellin treatment before infection decreased bacterial load in the lungs, likely due to an increase in neutrophil recruitment, and reduced signs of inflammation, including proinflammatory cytokines. The combination of flagellin and GNT showed a synergistic effect, decreasing even more the bacterial load and increasing mice survival rates, in comparison to mice pre-treated only with flagellin. These findings suggest that preventive nasal administration of flagellin could restore the effect of GNT against MDR strains of PA, paving the way for the use of flagellin in vulnerable patients with chronic respiratory diseases.

100 项与 Flagellin 相关的药物交易

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