Preclinical studies performed in mice, dogs and non-human primates (NHP) showed that vaccination was safe and stimulated strong immune responses in animals of different sexes and ages. Vaccinated animals were protected against a lethal challenge with a highly virulent T. cruzi strain. The vaccine also prevented chronic phase-associated damage in a sub-lethal early chronicity model. Vaccinated animals showed less tissue damage and electrocardiogram (ECG) abnormalities, and reduced parasite burden. Experiments addressing the potential of the vaccine in therapeutic setting alone and in combination with an antiparasitic drug confirmed the beneficial effects resulting from administering the novel combination therapy. Treated animals showed i) less alterations in the ECG, normal levels of enzymes indicating myocardium damage, less inflammation and fibrosis in skeletal and/or heart muscle; and ii) improved vaccine-specific immune responses. The acute and chronic infection models established in NHPs are also invaluable tools for evaluating future vaccines and therapies. Finally, the pivotal toxicology study conducted in rabbits showed no alterations in all tested parameters, thereby demonstrating vaccine non-clinical safety and paving the road towards clinical development.
From a manufacturing perspective, the optimization of a CDA cost-efficient enzymatic synthesis production process in large quantities (up to 5 million doses per batch) marks a critical step toward vaccine accessibility and commercial viability. Although some hurdles still need to be addressed for large scale clinical-grade Traspain antigen production, foundational work was laid for process optimization. The submission of a patent for an improved derivative of Traspain further strengthens the project's innovation and protects future commercial applications. Complementing this, the trademark “CRUZIVAX” was secured in major jurisdictions, reinforcing strategic positioning for future deployment.
Experiments also quantified the importance that patients living in endemic and non-endemic areas, and communities living in endemic areas attribute to the selected vaccine characteristics. Further, it was found that Chagas disease significantly reduces Health-Related Quality of Life, and that the long-term costs associated with the management of Chagas disease is a non-negligible resource burden. On the policy front, CRUZIVAX proactively engaged with national and regional stakeholders, held consultations with international bodies, and was presented in global forums, spearheading also discussions on cost-effective and innovative combination therapies for Chagas. A policy brief targeting non-research audiences is also being prepared to disseminate the project's health-economic implications and inform public health planning.
