Virus-like Particle Display of the alpha-Gal Epitope for the Diagnostic Assessment of Chagas Disease

The alpha-Gal antigen [Gal alpha(1,3)Gal beta(1,4)GlcNAc alpha] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of alpha-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors. The nanoparticle-alpha-Gal construct allowed for perfect discrimination between Chagas patients and the others, avoiding false negative and false positive results obtained with current state-of-the-art reagents. As previously reported with purified alpha-Gal-containing glycosylphosphatidylinositol-anchored mucins, the current study also showed concentrations of anti-alpha-Gal IgG to decrease substantially in patients receiving treatment with benznidazole, suggesting that the semiquantitative assessment of serum levels of this highly abundant type of antibody can report on disease status in individual patients.