Abstract:
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Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people
worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although
both are efficacious against the acute stage of the disease, this is usually asymptomatic
and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when
life-threatening heart and/or gut tissue disruptions occur in ∼30% of those chronically
infected. By then, the drugs’ efficacy is reduced, but not their associated high toxicity.
Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection
and/or the development of symptoms would be a breakthrough in the management
of the disease. Current vaccine candidates are mostly based on the delivery of single
antigens or a few different antigens. Nevertheless, due to the high biological complexity
of the parasite, targeting as many antigens as possible would be desirable. In this
regard, an epitope-based vaccine design could be a well-suited approach. With this
aim, we have gone through publicly available databases to identify T. cruzi epitopes
from several antigens. By means of a computer-aided strategy, we have prioritized a
set of epitopes based on sequence conservation criteria, projected population coverage
of Latin American population, and biological features of their antigens of origin. Fruit of
this analysis, we provide a selection of CD8+ T cell, CD4+ T cell, and B cell epitopes that
have <70% identity to human or human microbiome protein sequences and represent
the basis toward the development of an epitope-based vaccine against T. cruzi. |