UNIVERSAL IMMUNE SYSTEM SIMULATOR (UISS)
The Universal Immune System Simulator (UISS) is an agent-based model able to simulate with a high degree of accuracy the hallmarks of the human immune system. UISS uses a multi-layer approach that is basically considering three layers:
• the physiological response of the immune system to a non-self (or self in presence of immune system compromission) entity (physiology layer);
• the dynamics related to the progression of the disease (disease layer);
• eventually, the effects induced by different treatments on the control of the disease (treatment layer).
The multi-layer approach allows UISS to be easily adapted and extensively applied to a large set of biological scenarios, as an in silico trial, to predict the disease progression and/or the effect of immunotherapies
Reverse vaccinology (RV) conjugated with computational modelling and simulation can accelerate and facilitate the vaccine discovery pipeline. RV approaches have been developed to take advantage of pathogens genome sequence to narrow down the number of antigens for selecting the most suitable candidate. RV tools provide a score for predicted characteristics based on a manually chosen filter and rank. For example, to control a new possible pandemic due to genome recycling, RV can assist in accelerating the discovery of potential new targets that can be used in a vaccine formulation (or therapeutic one).
Climate change and melting glaciers are critical issues due to reactivating frozen viruses and emerging new pandemics. H5N1 is one of the potential strains present in frozen lakes that can raise a pandemic. Investigating structural antigen protein is the most profitable therapeutic pipeline to generate an effective vaccine against H5N1. In the perspective of advanced reverse vaccinology, the Universal Immune System Simulator, an in silico trial computational framework, was applied to estimate vaccine efficacy using a cohort of 100 digital patients.