Description du projet:
Antimicrobial resistance (AMR) is one of the major global public health threats according to the World Health Organization (WHO). It is estimated that in 2019 bacterial AMR was directly responsible for 1.27 million deaths worldwide and contributed to 4.95 million deaths. In the European Union, bacterial AMR are estimated to cause 35'000 deaths each year and the cost to the economy is significant: annual cost due to healthcare expenditures and productivity losses estimated at approximately '1.5 billion in the EU.
New treatments for bacterial infections are urgently needed. One possibility is the use of `lytic' bacteriophages, or phages for short, which are viruses that very specifically infect and kill bacteria. Phages exist naturally all over the planet and can be found in water, soil, or animals. Phages have been used since the beginning of the 20th century for the treatment of bacterial infections (so-called phage therapy) but were progressively replaced by antibiotics after the Second World War in Western countries. Nowadays phage therapy is again seen as one complimentary and realistic approach to fight against difficult-to-treat bacterial infections.
In this project, after successful technology transfer of a lab-scale Pseudomonas aeruginosa phage production process from the CHUV, Lausanne (Laboratory of Bacteriophages and Phage Therapy of Dr. Grégory Resch and Cell Production Center of Dr. Jean-François Brunet) to the Biofactory Competence Center (BCC) of the HEIA-FR, the process was characterized with a structured Quality-by-Design approach as outlined by the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use. The Critical Quality Attributes (CQAs) and Process Performance Attributes (PPAs) were identified based on the framework of requirements for Phage Therapy Medicinal Products (PTMPs) outlined in the European Pharmacopeia 11.6, general chapter 5.31 01/2025 © Council of Europe. A Failure Mode and Effects Analysis (FMEA) risk assessment that was performed to evaluate the criticality of process variables, including process parameters (PP) and material attributes (MA). This risk assessment served as the basis for the characterization and optimization studies of CHUV's P. aeruginosa phage production process. More precisely, the process variables with the highest potential influence on CQAs and/or PPAs were identified and further assessed for process characterization and optimization with Design of Experiment (DoE) studies. Results were already partially published in the journal Chimia in 2025 and presented in two conferences: ILMAC in September 2025 in Basel (Switzerland) and Viruses of Microbes conference in Prague in July 2026 (Th.
In addition, assessment of phage production with `patient strains' instead of standardized `production strains' was evaluated in order to give recommendations for commercial phage production processes.
For long term storage of phages at room temperature, lyophilization of the current final liquid formulation was assessed. Several excipients were tested, as well as the influence of lyophilization process parameters were evaluated. Results were presented at the JAFRAL Phage Summit 2026 in Ljubljana (Slovenia).
At HES-SO Valais, sequencing, assembly, and annotation of the phage genome was successfully implemented to confirm phage identity.
During the whole project, Dr. Grégory Resch from CHUV supported this project with his know-how in phage therapy and made available several P. aeruginosa phages with different morphologies for this project. P. aeruginosa is a gram-negative bacterium, which under certain conditions can be pathogenic. Highly resistant to conventional antibiotic treatment, it often causes nosocomial infections. The project focused on this pathogen since it is the main pathogen involved in lung infection of cystic fibrosis (CF) patients.
This collaboration with CHUV formed the basis for the submission of an
Research team within HES-SO:
Grandjean Jessica
, Brück Wolfram Manuel
, Wegmüller Sarah
, Emery Mabillard Martine
, Maillard Philippe
, Garcia Samuel
, Adler Aline
, Scotton Sarah
, Lehner Bruno
, Baudin Martine
, Jungo Rhême Carmen
Partenaires académiques: VS - Institut Sciences du vivant; FR - EIA - Institut ChemTech
Durée du projet:
01.01.2025 - 31.07.2026
Montant global du projet: 214'946 CHF
State: Ongoing
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