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Updated: Jan 7, 2026
Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections
Published on: August 30, 2014
Flagellin nebulization enhances respiratory immune responses in the porcine model
Mara Baldry1, Ignacio Caballero2, Lisette Ruuls3
1University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France.
Abstract:
Respiratory delivery of the Toll-like receptor 5-agonist FLAMOD, a recombinant flagellin, stimulates the airway epithelium, mobilizing immune cells and effectors in mouse models to combat respiratory infections, especially bacterial pneumonia. This study represents a comprehensive assessment of FLAMOD delivered by nebulization in pigs. A single nebulized dose was well tolerated with no adverse clinical effects. FLAMOD treatment led to immune cell infiltration in the lung tissue and granulocyte recruitment in conducting airways, as shown by histology and flow cytometry. RNA sequencing established immune activation across the respiratory tract, from the nose, trachea, and bronchi to the lungs, highlighting innate immunity, bacterial defense, cytokine and chemokine signaling, and granulocyte chemotaxis as key biological pathways. These findings demonstrate that FLAMOD stimulates a robust and common respiratory immunity, as well as compartment-specific response, providing a proof-of-concept for inhalation-based therapeutic strategies to combat bacterial pneumonia in the clinical setting.
Insights
Nebulized FLAMOD, a Toll-like receptor 5 agonist, safely stimulates respiratory immunity in pigs. This approach shows promise for treating bacterial pneumonia through enhanced innate immune responses in the airways.
Area of Science:
- Immunology
- Respiratory Medicine
- Pharmacology
Background:
- Toll-like receptor 5 (TLR5) agonists, like flagellin, activate innate immunity.
- Respiratory infections, particularly bacterial pneumonia, pose significant health challenges.
- FLAMOD, a recombinant flagellin, has shown potential in mouse models for respiratory infections.
Purpose of the Study:
- To comprehensively assess the safety and immunogenicity of nebulized FLAMOD in pigs.
- To investigate the immune response elicited by FLAMOD across the entire respiratory tract.
- To establish a proof-of-concept for inhalation-based FLAMOD therapy against bacterial pneumonia.
Main Methods:
- Pigs were administered a single nebulized dose of FLAMOD.
- Histology and flow cytometry were used to analyze immune cell infiltration and recruitment in lung tissue and airways.
- RNA sequencing was performed on samples from the nose, trachea, bronchi, and lungs to assess immune gene expression.
Main Results:
- A single nebulized dose of FLAMOD was well-tolerated with no observed adverse clinical effects.
- FLAMOD treatment induced significant immune cell infiltration in lung tissue and granulocyte recruitment in conducting airways.
- RNA sequencing revealed broad immune activation across the respiratory tract, involving innate immunity, bacterial defense, cytokine/chemokine signaling, and granulocyte chemotaxis.
Conclusions:
- Nebulized FLAMOD is safe and effectively stimulates a robust, common, and compartment-specific respiratory immune response in pigs.
- FLAMOD demonstrates potential as an inhalation-based therapeutic strategy for combating bacterial pneumonia.
- These findings support further development of FLAMOD for clinical application in respiratory infections.
