Consensus Enolase of Trypanosoma Cruzi: Evaluation of Their Immunogenic Properties Using a Bioinformatics Approach

Abstract

There is currently no vaccine against American trypanosomiasis, caused by the parasite Trypanosoma cruzi. This is due to the genomic variation observed in the six DTUs of T. cruzi. This work aims to propose a consensus sequence of the enolase protein from different strains of T. cruzi and mainly evaluate its immunogenic properties at the bioinformatic level. From specialized databases, 15 sequences of the enolase gene were aligned to obtain a consensus sequence, where this sequence was modeled and then evaluated and validated through different bioinformatic programs to learn their immunogenic potential. Finally, chimeric peptides were designed with the most representative epitopes. The results showed high immunogenic potential with six epitopes for MHC-I, and seven epitopes for MHC-II, all of which were highly representative of the enolase present in strains from the American continent as well as five epitopes for B cells. Regarding the computational modeling, molecular docking with Toll-like receptors showed a high affinity and low constant of dissociation, which could lead to an innate-type immune response that helps to eliminate the parasite. In conclusion, the consensus sequence proposed for enolase is capable of providing an ideal immune response; however, the experimental evaluation of this enolase consensus and their chimeric peptides should be a high priority to develop a vaccine against Chagas disease.

Targeting <em>Plasmodium </em>Population Bottlenecks with Parasite Ligands as Vaccine Antigens

“…A. marginale AmEno01 protein was identified as a vaccine candidate, as it exists across all groups of A. marginale strains with well-conserved 3D-structures [58]. Bioinformatics studies of enolase in Trypanosoma cruzi, a causative agent of American trypanosomiasis, identified a consensus sequence of the enolase protein from 15 T. cruzi strains as a vaccine candidate [59].…”

Chagas Heart Disease: Beyond a Single Complication, from Asymptomatic Disease to Heart Failure

“…Immunological protection against T. cruzi has been studied since the second decade of the last century using animal models in which immunogens from killed parasites, attenuated parasites, cell fractions, purified proteins, and nucleic acid vaccines have been tested [162]. One of the most recent proposals for the development of a vaccine is the bioinformatics approach, which employs a wide range of computational techniques, including sequence and structural alignment, database design and data mining, macromolecular geometry, phylogenetic tree construction, prediction of protein structure and function, gene finding, and expression data clustering with the goal of functional analysis and data mining of data sets leading to biologically interpretable results and insights; recently this tool has been applied to the field of vaccinology against T. cruzi with promising results [192].…”