Enhancing In Silico Protein-Based Vaccine Discovery for Eukaryotic Pathogens Using Predicted Peptide-MHC Binding and Peptide Conservation Scores
نویسندگان
چکیده
Given thousands of proteins constituting a eukaryotic pathogen, the principal objective for a high-throughput in silico vaccine discovery pipeline is to select those proteins worthy of laboratory validation. Accurate prediction of T-cell epitopes on protein antigens is one crucial piece of evidence that would aid in this selection. Prediction of peptides recognised by T-cell receptors have to date proved to be of insufficient accuracy. The in silico approach is consequently reliant on an indirect method, which involves the prediction of peptides binding to major histocompatibility complex (MHC) molecules. There is no guarantee nevertheless that predicted peptide-MHC complexes will be presented by antigen-presenting cells and/or recognised by cognate T-cell receptors. The aim of this study was to determine if predicted peptide-MHC binding scores could provide contributing evidence to establish a protein's potential as a vaccine. Using T-Cell MHC class I binding prediction tools provided by the Immune Epitope Database and Analysis Resource, peptide binding affinity to 76 common MHC I alleles were predicted for 160 Toxoplasma gondii proteins: 75 taken from published studies represented proteins known or expected to induce T-cell immune responses and 85 considered less likely vaccine candidates. The results show there is no universal set of rules that can be applied directly to binding scores to distinguish a vaccine from a non-vaccine candidate. We present, however, two proposed strategies exploiting binding scores that provide supporting evidence that a protein is likely to induce a T-cell immune response-one using random forest (a machine learning algorithm) with a 72% sensitivity and 82.4% specificity and the other, using amino acid conservation scores with a 74.6% sensitivity and 70.5% specificity when applied to the 160 benchmark proteins. More importantly, the binding score strategies are valuable evidence contributors to the overall in silico vaccine discovery pool of evidence.
منابع مشابه
In silico identification of epitopes from house cat and dog proteins as peptide immunotherapy candidates based on human leukocyte antigen binding affinity
The objective of this descriptive study was to determine Felis domesticus (cat) and Canis familiaris (dog) protein epitopes that bind strongly to selected HLA class II alleles to identify synthetic vaccine candidate epitopes and to identify individuals/populations who are likely to respond to vaccines. FASTA amino acid sequences of experimentally validated allergenic proteins of house cat and d...
متن کاملPlant-based expression systems for protein and antimicrobial peptide production
Molecular farming technology offers a unique advantage that almost any protein can be produced economically and safely under very controlled conditions. Besides traditional production systems, such as bacteria, yeasts, insects and mammal cell lines, plants can now be used to produce eukaryotic recombinant proteins, especially therapeutic ones. Their advantages as hosts for protein production in...
متن کاملOptimization of a Method to Prepare Liposomes Containing HER2/Neu-Derived Peptide as a Vaccine Delivery System for Breast Cancer
The purpose of this study was to optimize a method for the encapsulation of P5 peptide, a new designed peptide containing MHC class I epitopes from rat HER2/neu protein, into liposomes as an approach for breast cancer vaccine formulation. The efficiency of liposomal encapsulation of peptides is generally low and development of an optimized method to increase encapsulation efficiency is a big ch...
متن کاملOptimization of a Method to Prepare Liposomes Containing HER2/Neu-Derived Peptide as a Vaccine Delivery System for Breast Cancer
The purpose of this study was to optimize a method for the encapsulation of P5 peptide, a new designed peptide containing MHC class I epitopes from rat HER2/neu protein, into liposomes as an approach for breast cancer vaccine formulation. The efficiency of liposomal encapsulation of peptides is generally low and development of an optimized method to increase encapsulation efficiency is a big ch...
متن کاملComputer-aided vaccine designing approach against fish pathogens Edwardsiella tarda and Flavobacterium columnare using bioinformatics softwares
Edwardsiella tarda and Flavobacterium columnare are two important intracellular pathogenic bacteria that cause the infectious diseases edwardsiellosis and columnaris in wild and cultured fish. Prediction of major histocompatibility complex (MHC) binding is an important issue in T-cell epitope prediction. In a healthy immune system, the T-cells must recognize epitopes and induce the immune respo...
متن کامل