Prof. Dr. Liam O’Mahony
Principal Investigator Molecular Immunology at the Swiss Institute of Allergy and Asthma Research and Professor of Immunology at APC Microbiome Ireland.
The Roles of Microbes and their Metabolites in Allergic Immune Responses
The influence of microbiome composition and metabolic activities on human health throughout life is, by now, a well-established research and clinical concept. Significant progress has been made on elucidating these interactions, but there are still many unresolved and challenging questions remaining. In this presentation, I will provide an overview of the fundamentals of mucosal immunological responses to microbes and how our understanding of this field has changed in recent years. In addition, I will review microbiome/host interactions and the mechanisms by which these interactions influence allergic responses. Finally, I will identify the areas where we need to focus our future basic research activities in order to progress the clinical understanding of the microbiome’s influence on health, especially in immune development and allergy prevention.
Prof. Dr. Jeffrey Beekman
Professor Cellular Disease Models and Principal Investigator of Cystic Fibrosis research lab of the Department of Pediatrics at University Medical Center Utrecht.
Intestinal organoids and the modelling of CF disease
Prof. Beekmans lab aims to develop cellular disease models that capture human disease and therapy thereof. Such models are used in a preclinical context to identify new biology, new treatment options or mode-of-actions of treatments for various genetic diseases. In the clinical domain, we explore how patient cells can be used as a living biomarker to support individual clinical decision making (e.g. personalized treatment) or to help stratify patients for clinical trials with new drug candidates. His research has focussed on cystic fibrosis, but is currently expanding to other genetic diseases. Cystic fibrosis is a genetic disease that affects epithelial defence mechanisms against pathogens, which lead to chronic infections of the lungs and strongly reduced quality of life and life expectancy. New treatments that target the root cause are being developed, but their exact mode of actions and individual efficacy remain unclear. His work on intestinal organoids and the modelling of CF disease showed for the first time that biobanks of patient-derived stem cell cultures could be used to identify patients with rare variants of CF that could benefit from these treatments, leading to individual access and reimbursement. This work has been awarded by multiple prestigious international awards, and the application of organoids for personalized medicine of CF is currently implemented worldwide.
Prof. Dr. Leo James
Principal Investigator MRC, Medical Research Council Laboratory of Molecular Biology at the University of Cambridge.
Trim-Away: Targeted degradation of pathogens and proteins by the cytosolic antibody receptor TRIM21
Viruses are masters of rapid change, adapting and evolving within days. In contrast, our immune system evolves slowly over decades. Antibodies are the exception to this rule and the only molecule we make that targets viruses and evolves on the same timescale. But viruses have a second trick; they replicate inside our cells and away from antibodies circulating in the blood. At least this was the view for over a century. In my talk, I will describe the recent discovery that there is a system of intracellular antibody immunity that protects us from infection. During infection, antibodies stick to circulating viruses and accompany them into cells. Once inside the cell, antibody-coated viruses are detected by an enzyme called TRIM21. TRIM21 tags each virus for destruction in the proteasome, the cell’s recycling machine. TRIM21 is found in every cell in the body, ready to destroy not only diverse viruses but also proteopathic neurodegenerative agents like tau. I will discuss how we are learning about this system in order to better understand infection and inspire new therapeutics and biotechnology. An example of this is ‘Trim-Away’, a technology in which TRIM21 is used to rapidly degrade specific cell proteins instead of viruses. This technology offers an alternative to siRNA or CRISPR but with the advantage that it removes existing proteins within hours. While Trim-Away is currently used as a research tool, it could be adapted in the future into a new type of therapeutic to treat a wide range of diseases
Prof. Dr. Willem Mulder
Professor of Precision Medicine at the department of Biomedical Engineering of Eindhoven University and Professor Radiology and Oncological Sciences at Mount Sinai’s Translational and Molecular Imaging Institute (TMII, Icahn School of Medicine, New York, USA).
Therapeutic targeting of innate immunity with nanobiologics
Immunotherapy is revolutionizing the treatment of diseases. Most of the immunotherapy strategies currently being developed engage the adaptive immune system. In recent years, emerging evidence has shown that the innate immune system displays long-term changes in its functional program through metabolic and epigenetic programming of myeloid cells (monocytes, macrophages, dendritic cells). Therefore, targeting myeloid cells and their progenitors is a powerful ‘therapeutic framework’ to regulate the delicate balance of immune homeostasis, priming/training and tolerance. This Presentation will showcase how nanobiologic-based immunotherapies can be applied to achieve long-term therapeutic benefits in detrimental diseases, including cancer and cardiovascular diseases as well as to prevent organ rejection after transplantation. In addition, a translational workflow involving innovative multimodality imaging approaches and large animal models will be discussed.
Prof. Dr. Xavier Saelens
Professor at the department of Biochemistry and Microbiology at Ghent University and Principal Investigator VIB-UGent Medical Biotechnology Center.
A universal influenza A vaccine based on the extracellular domain of the M2 protein
Influenza and human respiratory syncytial virus (RSV) infections can cause serious disease. Currently used influenza vaccines have moderate and variable efficacy, whereas there is no licensed vaccine yet against RSV. Our laboratory has focused on the highly conserved extracellular domain of Matrix protein 2 (M2e) of influenza A viruses to develop a universal influenza A vaccine candidate. Protection induced by M2e-vaccines against influenza A virus challenge is very broad and primarily mediated by non-neutralizing M2e-specific IgG that can activate FcÎ³ Receptors on alveolar macrophages. In vitro, this mode of protection can be mimicked and quantified in an antibody-dependent cellular phagocytosis assay using murine or human sera that contain M2e-specific IgG. More recently, we also generated M2e-targeting antibody-based biologicals with therapeutic anti-influenza A potential.The Influenza neuraminidase (NA) is a variable antigen that is largely neglected in currently used influenza vaccines. In collaboration with a private partner, we demonstrated that pan-N1 subtype NA immunity can be induced by computationally guided consensus recombinant NA antigens. In addition, we recently demonstrated that NA-specific antibodies that lack NA inhibiting activity can protect against influenza through Fc-mediated effector mechanisms.
Our lab has also explored an unconventional approach to develop a vaccine candidate against RSV by focusing on the extracellular domain of the small hydrophobic protein (SHe) of this virus. We showed that a SHe-fusion construct can induce SHe-specific antibodies that strongly reduce RSV replication in challenged mice and cotton rats. A phase 1 clinical study in older adults revealed that an adjuvanted SHe peptide vaccine was well tolerated and could induce SHe-specific IgG titers that were sustained for more than a year.
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