Abstract

Epitope prediction is becoming a key tool for vaccine discovery. Prospective analysis of bacterial and viral genomes can identify antigenic epitopes encoded within individual genes that may act as effective vaccines against specific pathogens. Since B-cell epitope prediction remains unreliable, we concentrate on T-cell epitopes, peptides which bind with high affinity to Major Histacompatibility Complexes (MHC). In this report, we evaluate the veracity of identified T-cell epitope ensembles, as generated by a cascade of predictive algorithms (SignalP, Vaxijen, MHCPred, IDEB, EpiJen), as a candidate vaccine against the model pathogen uropathogenic gram negative bacteria Escherichia coli (E-coli) strain 536 (O6:K15:H31). An immunoinformatic approach was used to identify 23 epitopes within the E-coli proteome. These epitopes constitute the most promiscuous antigenic sequences that bind across more than one HLA allele with high affinity (IC50 < 50nM). The reliability of software programmes used, polymorphic nature of genes encoding MHC and what this means for population coverage of this potential vaccine are discussed.

Highlights

  • IntroductionVaccination is principally concerned with humoral and cell mediated adaptive immune responses [1]

  • Human immunity comprises the innate and the adaptive immune response

  • The Major Histacompatibility Complex (MHC) is a large region encoded on human chromosome 6; genes of the MHC are known as Human Leukocyte Antigens (HLA), and demonstrate the highest levels of sequence polymorphism within the human population [2]

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Summary

Introduction

Vaccination is principally concerned with humoral and cell mediated adaptive immune responses [1]. The overall goal is the generation of long lasting immunity against microbial pathogens via the production of diverse immune memory cells. The Major Histacompatibility Complex (MHC) is a large region encoded on human chromosome 6; genes of the MHC are known as Human Leukocyte Antigens (HLA), and demonstrate the highest levels of sequence polymorphism within the human population [2]. This genetic diversity is responsible for the adaptability of the human immune system to microorganisms and pathogens

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