ADVOCATE: Advanced complexity in human derived organoid models for virology

Understanding neurological infectious diseases is needed as they are a major threat to human health. Poliovirus has led to debilitating outbreaks of paralytic disease, and polio-related enteroviruses are still the most common causes of viral brain infections. Neuro-infections lead to high hospitalization rates and long-term complications with often no treatment available. Neuropathogenicity of human viruses is notoriously difficult to study in animal models. Therefore, suitable human experimental models are needed such as organoids, which accurately mimic the human physiological environment. In the ADVOCATE project, Amsterdam UMC and VectorY characterized a stem cell-derived neuromuscular organoid model for studying non-polio enteroviruses. Further, this model was infected with two non-polio enteroviruses and we confirmed the ability of these viruses to infect neurons. Finally, we used neural organoids to study the uptake and spread of vectors that are used for delivering therapeutic antibodies. The results from the ADVOCATE study further increased our understanding of enterovirus pathogenesis and will be useful in the design of therapeutic antibodies in the further. Moreover, our model will lower the barriers for the implementation of human disease models in virology and enable a smooth transition to animal-free innovation.