In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease

Abstract

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.

Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach

“…Selection of an appropriate epitope-specific linker (e.g., flexible, rigid, cleavable) is an essential step in designing an immunogenic multi-epitope vaccine so that the domains can work independently avoiding interaction and interference between them [132,133]. We chose linkers based on their length and rigidity-flexibility properties and in accordance with some previous studies [68,[134][135][136][137][138][139][140][141]. However, the precise order and position of the epitopes and spacers need to be elucidated through experimental evidences.…”

An Overview of Current Uses and Future Opportunities for Computer-Assisted Design of Vaccines for Neglected Tropical Diseases

“…In search of potentially good epitopes to encompass a vaccine ensemble, protein invariability has been considered to be a major attribute. 23 , 24 , 54 , 55 A hypothetical vaccine product providing pan-protection against multiple strains of a circulating pathogen would indeed be a much desirable characteristic considering the very limited resources for vaccine development, especially for NTDs. Therefore, an initial step to find out the best epitopes often entails using CD-HIT or other BLAST-like tools to cluster together all the proteins from the different proteomes or strains of the pathogen in question, in order to reduce their redundancy ( Figure 2 ).…”

“… 59 An alternative approach for B-cell epitopes prediction is to rely on 3D protein structures where it is possible to identify regions accessible to antibody recognition through relative solvent accessibility calculations (eg, using NACCESS 64 ), as well as determining the flexibility of such regions by analyzing the temperature factors, or B-factors, of residues within 3D structures. 23 , 24 These factors are included in .pdb files downloaded from the Protein Data Bank, 65 and are a measure of the smearing in a protein structure due to the motions of its atoms: the higher this value is, the higher the flexibility. 66…”

A comparative genomics and immunoinformatics approach to identify epitope-based peptide vaccine candidates against bovine hemoplasmosis

“…Since bovine hemoplasmas show significant differences at genomic level and they impact in cattle health causing economic losses, we decided to perform an immune-informatic analysis to identify B-cell epitopes that could be used in the design of potential vaccines to prevent bovine hemoplasmosis. The development of vaccines based on this strategy has been successfully used to prevent some diseases in human and animals, including the cytoplasmic protein subolesin used to prevent infestations of tick Rhipicephalus microplus [37][38][39][40]. The immune-informatics analysis predicts several B-cell epitopes (Table 3), which could be used in the design of molecular detection methods and vaccines.…”