title: Identification of CD4+ T-cell epitope and investigation of HLA distribution for the immunogenic proteins of Burkholderia pseudomallei using in silico approaches - A key vaccine development strategy for melioidosis.
abstract: Melioidosis is a serious infectious diseases affecting multi-organ system in humans with high mortality rate. The disease is caused by the bacterium, Burkholderia pseudomallei and it is intrinsically resistant to many antibiotics. Thus, there is an urgent need for protective vaccine against B. pseudomallei; which may reduce morbidity and mortality in endemic areas. The identification of peptides that bind to major histocompatibility complex II class helps in understanding the nature of immune response and identifying T-cell epitopes for the design of new vaccines. Previous studies indicate that, ompA, bipB, fliC and groEL proteins of B. pseudomallei stimulate CD4+ T-cell immune response and act as protective immunogens. However, the data for CD4+ T-cell epitopes of these immunogenic proteins are very limited. Hence, in this present study we attempted to identify CD4+ T-cell epitopes in B. pseudomallei immunogenic proteins using in silico approaches. We did population coverage analysis for these identified epitopic core sequences to identify individuals in endemic areas expected to respond to a given set of these epitopes on the basis of HLA genotype frequencies. We observed that eight epitopic core sequences, two from each immunogenic protein, were associated with the maximum number of HLA-DR binding alleles. These eight peptides are found to be immunogenic in more than 90% of population in endemic areas considered. Thus, these eight peptides containing epitopic core sequences may act as probable vaccine candidates and they may be considered for the development of epitope-based vaccines for melioidosis.
authors.affiliation: Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India.
authors.forename: Rayapadi G
authors.initials: RG
authors.lastname: Swetha
authors.affiliation: Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India.
authors.forename: Madangopal
authors.initials: M
authors.lastname: Sandhya
authors.affiliation: Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India.
authors.forename: Sudha
authors.initials: S
authors.lastname: Ramaiah
authors.affiliation: Medical & Biological Computing Laboratory, School of BioSciences and Technology, VIT University, Vellore 632014, India. Electronic address: aanand@vit.ac.in.
authors.forename: Anand
authors.initials: A
authors.lastname: Anbarasu
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D010455:Peptides / Q000235:genetics / Q000276:immunology; D015203:Reproducibility of Results
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D010455:Peptides
keywords: Burkholderia pseudomallei; Epitope; Melioidosis; Population coverage; Vaccine