GVN Center and Member Spotlight
Head, Division of Experimental Medicine, Department of Internal Medicine at the Radboud University Medical Center.
Director, GVN Center of Excellence
What are you and your institution currently working on regarding COVID-19?
At the Radboud University Medical Center, Nijmegen, the Netherlands, several important COVID-19 related research projects are currently underway. At the diagnostic level, we coordinate a large collaboration project with 7 regional hospitals to build a database and biobank of clinical data and samples from patients with COVID-19, aimed to discover and inform about biomarkers of severity in COVID-19 patients at both immunological and radiological levels. As innovative therapeutic approaches, researchers in our centers have initiated several important clinical trials of immunotherapies (i.e., anti-IL-1 and anti-IL-6 therapies), the kallikrein system (icatibant and lanadelumab therapies), and angiotensin receptor antagonists. Finally, other important goal of our research is the prevention of COVID-19 through vaccination. Our focus is not only on specific vaccines but also on repurposing known vaccines through induction of heterologous and trained immunity.
What is your role and significance in the study of innate, ‘trained immunity’ from your research?
Trained immunity facilitates the functional reprogramming of innate immune cells that induces long-term heterologous protection against various infections after a mild infection or vaccination. Of course, this immunity provides a partial protection, and does not provide protection to any type of secondary infection. We try to decipher specific mechanisms behind this important immune property of some live attenuated vaccines that are able to provide non-specific protection against infections. A better understanding of this trained immunity will enable us not only to develop novel and potent heterologous vaccines on the one hand, but also to utilize trained immunity to enhance the effectiveness of classical vaccines. The availability of effective heterologous vaccines can be important to prepare for emerging pathogens and future pandemics.
My team’s research goal is to translate information obtained through the in-depth assessment of immune responses in health and disease into novel diagnostic and therapeutic approaches in patients. My team has a strong track record on translating immunological and genetic information into understanding pathophysiological mechanisms of disease. We have broad expertise in the host mechanisms responsible for the recognition of viral and bacterial pathogens and the activation of the innate immune system. We have described the epigenetic mechanisms mediating innate immune memory (‘trained immunity’) for the first time, and their role in vaccination, infection, immune-mediated diseases, and cancer. I am also the coordinator of the International Trained Immunity Consortium that aims to understand the processes of innate immune memory, and develop prevention and therapeutic approaches based on trained immunity. His work led to the first phase III clinical trial using vaccination with a live attenuated vaccine (BCG) as a prevention strategy against infections (including viral) in the elderly. In addition, the concept of trained immunity is at the basis of large phase III clinical trials using live attenuated vaccines in COVID-19.