Objectives

The strategic goal of the CRUZIVAX project is to develop Traspain as a prophylactic intranasal needle-free vaccine candidate adjuvanted with c-di-AMP against Trypanosoma cruzi infection

Chagas is a neglected disease endemic in 21 Latin-American countries caused by Trypanosoma cruzi. It is the largest parasitic disease burden in the Americas (>11,000,000 chronic infections) and the first cause of cardiac morbidity in poor rural/suburban areas. It became a worldwide concern as a result of mass migration with reports in 19 non-endemic areas (>1.3 million carriers in EU/USA). Treatment is difficult since acute infections have mild symptoms and remain largely unnoticed evolving to chronicity. Drug therapy is also long, often associated with side effects (10-30% interruption) and only active during early infection. The main objective of CRUZIVAX is to bridge the gap between preclinical and clinical development by performing preclinical and clinical phase 1 studies of a needle-free vaccine against T. cruzi with proven efficacy in preclinical models. The vaccine is based on a structure-engineered trivalent chimeric antigen lacking immune decoy sequences and an adjuvant (c-di-AMP) promoting self-limited locally-restricted immune activation stimulating humoral and cellular immunity, which is expected to protect as prophylactic or therapeutic (combined with Benznidazole) vaccine. To achieve this CRUZIVAX will: (i) conduct preclinical studies to assess immunogenicity and efficacy of different vaccine formulations in prophylactic and therapeutic settings, (ii) produce cGMP antigen and adjuvant by cost-efficient manufacturing (facilitated uptake by health systems with limited resources), (iii) perform a preclinical safety assessment of the vaccine, (iv) conduct a phase 1 vaccine clinical trial in healthy volunteers, and (v) carry out a health economics analysis to identify critical target-product profile parameters. The vaccine will strengthen the pipeline of products for Chagas disease, aimed at reducing disease burden and its social and economic impact.