VIB, Flanders’ leading life sciences institute, and UGent are leading a European Network that has secured a grant of more than 8 million euros to develop a new vaccine technology against bacterial infections. In a consortium called "Baxerna," VIB, UGent, Ghent University Hospital, VUB, ULB, the Pasteur Institute, the Radboud Medical Center and the Karolinska Institute, led by Profs. Lennart Martens and Francis Impens (VIB-Ghent University Center for Medical Biotechnology) will search for new antibacterial mRNA vaccines as a preventive tool in the fight against antimicrobial resistance. This will initially focus on pathogens such as Mycobacterium tuberculosis, Mycobacterium ulcerans and Acinetobacter baumannii. The first clinical studies will take place at Ghent University Hospital in collaboration with the Center for Vaccinology (CEVAC).

Antimicrobial resistance (AMR) occurs when bacteria or other microorganisms such as viruses, fungi and parasites no longer respond to antibiotics. The phenomenon has long been of concern to the medical community as the WHO previously proclaimed antimicrobial resistance as one of the top 10 most important threats to global public health. After all, AMR could mean that conventional medicines are no longer sufficient to treat infections and that surgical procedures and cancer treatments could become extremely dangerous in the future because of the risk of infection with resistant germs.

Data shows that more than 1 million people worldwide die each year from infections caused by drug-resistant bacteria. That figure will only increase without action: without new treatments, AMR is expected to kill more people than cancer by 2050. To respond to this growing social need, thanks to a European grant of 5.3 million euros, VIB and Ghent University will now combine their expertise in advanced mass spectrometry, artificial intelligence, immunopeptidomics and experience in mRNA vaccine technology to develop preventive antibacterial vaccines. Such vaccines could contribute to the prevention of bacterial infections, further reducing the consumption of antibiotics. Together with research funding from VUB, the grant represents an injection of nearly 6 million euros into Flemish vaccine research.

Anticipating the defenses of bacteria

The current generation of antibacterial vaccines is developed based on attenuated or dead bacteria formulated as antigens that can trigger an immune response in our bodies. While such vaccines already appear to work well against extracellular bacteria – bacteria that move between our cells in our bodies – a major challenge still lies with the so-called intracellular bacteria, which can enter a cell and thus better shield themselves from the immune system.

Our body can attack such infections because it can recognize tiny bits of peptides, fragments of broken-down bacterial proteins, on the surface of infected cells. This allows our immune system to clear infected cells anyway. Consequently, unraveling those antigenic peptides and the bacterial proteins from which they originate is crucial to developing effective vaccines against intracellular bacteria. Once known, and thanks to the expertise of Prof. Karine Breckpot (VUB), such antigenic proteins can be encoded in mRNA. Subsequently, mRNA vaccines can in turn train our immune system to attack infected cells already at a very early stage of infection. That is where the consortium now hopes to make progress.

Francis Impens, VIB-UGent Center for Medical Biotechnology: "With Baxerna, we can finally look ahead to new ways to develop antibacterial vaccines. Together with Prof. Martens' lab, we can use advanced mass spectrometry and artificial intelligence to identify and analyze bacteria-specific antigenic proteins. Based on that, we can design an RNA molecule encoded for a specific bacterial antigen. In turn, that RNA molecule can form the basis of a vaccine, allowing us to preemptively train our immune system against such infections."

Cutting-edge technology and international expertise

For this ambitious project, the Baxerna consortium brings together the expertise of numerous research institutions. Not in the least, the local Ghent expertise in nanotechnology and more specifically in the formulation of mRNA vaccines plays an important role. For this, Baxerna relies on the research groups of Dr. Ine Lentacker and Prof. Stefaan De Smedt of Ghent University. The close collaboration between VIB, Ghent University, and Ghent University Hospital reflects the ambition to grow into a leading academic and clinical center for the development of advanced cell and gene products. GATE, the Ghent multidisciplinary platform for bench-to-bedside translational gene and cell therapy, supports this ambition.

Thanks to UGent's participation, Baxerna can also rely on a proprietary mRNA vaccine technology in which a bacterial adjuvant particle is added to the vaccines, allowing a broader and stronger immune response to be elicited. In addition to UGent and VUB, immunology experts from the French Pasteur Institute and the Dutch Radboud Medical Center will be involved to study in detail the immune response to the mRNA vaccines. Preclinical safety and potency testing will be done at the Karolinska Institute in Sweden.

In addition, the consortium has the ambition to develop a pipeline of antibacterial mRNA vaccines that can be tested for the first time in clinical studies at the Ghent University Hospital. These studies will be conducted in collaboration with Ghent University Hospital and Isabel Leroux-Roels of CEVAC. Candidate vaccines for tuberculosis will initially be developed and tested in a Phase I clinical trial at Ghent University Hospital and in collaboration with CEVAC under the direction of Isabel Leroux-Roels.

Francis Impens, VIB-Ghent University Center for Medical Biotechnology