FLAGELLIN AEROSOL THERAPY AS AN IMMUNOMODULATORY ADJUNCT TO THE ANTIBIOTIC TREATMENT OF DRUG-RESISTANT BACTERIAL PNEUMONIA (FAIR)

Pneumonia is a type of respiratory tract infection that causes the lung, particularly the small air sacs called alveoli, to become inflamed making it difficult to breathe. Despite often being preventable, pneumonia is the third leading cause of death worldwide and it especially affects children and the elderly.

As pneumonia is predominantly caused by infection of the lungs by viruses or bacteria, a major complicating factor towards successful treatment is the emergence of antimicrobial resistance (AMR), where the bacteria causing pneumonia are resistant to the antibiotics used to treat and clear the infection. The World Health Organization estimates that bacterial infections due to AMR will become the leading cause of death worldwide by 2050 and thus effective alternative therapeutics are needed. To this end, the FAIR consortium aims to investigate therapies that may be used as an alternative to antibiotic treatment for pneumonia.

The FAIR strategy is to investigate the delivery of a host-directed adjunct therapeutic, namely flagellin, to infected tissue in order to enhance the effectiveness of first-line antibiotics in antibiotic-resistant pneumonia. Direct delivery to the airways using a nebulizer will allow stimulating lung innate immune defences, which are universal and have broad spectrum antimicrobial effects. This approach should avoid systemic adverse outcomes and concentrate the therapeutic effect at the target site of infection.

The FAIR consortium will employ a multidisciplinary approach to bring forward the use of flagellin as an adjunct therapeutic for antibiotic-resistant pneumonia. FAIR will use intricate in vitro and in vivo models to better understand the molecular and cellular signatures of protection in blood cells and respiratory tissues during treatment, while mathematical modelling will be used to identify markers that better predict response to standard antibiotic therapies and the boosting of innate immune defences.

At a translational level, from laboratory to clinic, safety of flagellin administration will be addressed during a Phase I clinical trial using the respiratory route. FAIR will also examine the adjunct therapy’s acceptability by patients and healthcare professionals. Finally, FAIR will use health economic modelling to assess the potential for nebulized flagellin to be a cost-effective, affordable adjunct to conventional treatment of AMR pneumonia in European healthcare systems.

Read "FAIR Ambitions"