New in silico trials look to fast-forward development of tuberculosis vaccine
Tuberculosis (TB) is one of the world’s deadliest diseases, killing 1.6 million people in 2021. While most TB cases are found in the developing world, developed countries are by no means immune. In fact, the rise in multidrug-resistant (MDR) TB increases the threat of a global outbreak. Although there is some evidence that a vaccine could help strengthen the immune system’s response to the disease, the development of such a shot has been constrained by high costs and long trial periods. But what if the answer to streamlining this entire process could be found in technology? That’s what the EU-funded STriTuVaD project intended to find out. “To tackle this dreadful disease, we aimed to deliver the computational simulations and virtual patients needed to fast-forward the development, testing and approval of a very promising vaccine,” says Epifanio Fichera, project manager at Etna Biotech, the project’s lead partner. This project’s prospective computational model validation is done in parallel with the double-blind, randomised clinical trials’ phase IIb of the RUTI® vaccine, one of the most advanced therapeutic vaccines against several forms of TB.
Using in silico trials
Traditionally, vaccine development involves conducting multiple clinical trials to determine safety and efficacy, which can take years and cost millions. “In silico trials, on the other hand, have the potential to simulate the effects of a vaccine in a virtual environment, which can help researchers identify the most promising vaccine candidates early on in the development process,” notes Fichera. In building its in silico trial, the project started using the pre-existing Universal Immune System Simulator (UISS) modelling framework, which can reproduce the dynamics of the human immune system at a large scale. Then, researchers from the University of Catania, supported by TBVI’s experts and all the other project partners, extended the UISS model to simulate how TB interacts with the immune system. Not only did this extended platform enable researchers to simulate artificial immunity induced by vaccinations and treatments for TB, but it also allowed them to create a library of virtual subjects and virtual vaccinated patients. Parallel to this work, researchers at the University of Sheffield were busy developing a Bayesian model capable of combining data from real patients with that of the aforementioned virtual patients. This was then integrated into the STriTuVaD platform to allow users to predict the effects of long-term combined therapy.
Promising initial outcomes
With Archivel Farma having completed the manufacturing and testing of a clinical batch of its RUTI® vaccine, it was time to put the STriTuVaD platform to the test. While AIIMS conducted the phase IIb clinical trial, the University of Catania used the platform to reproduce it virtually, testing the vaccine against drug-sensitive (DS) TB and MDR TB. At the same time, the University of Bologna addressed regulatory issues for the in silico approach. The DS-TB cohort reported no serious adverse events with the vaccine’s use and the MDR-TB study is currently advancing. Efficacy results from the clinical investigation will be published shortly. Based on these promising initial outcomes, along with its verification and validation, the STriTuVaD in silico trial platform has been released as software-as-a-service. “The public release of the STriTuVaD in silico trial platform to predict the efficacy of a vaccine against tuberculosis has the potential to revolutionise vaccine development,” concludes Fichera. “It represents an exciting and significant step forward in the fight against tuberculosis and other vaccine-preventable diseases.”
Keywords
STriTuVaD, in silico trials, tuberculosis, tuberculosis vaccine, vaccine, TB, disease
