In silico identification of universal HLA stimulating b and T-cell restricted mage epitopes for vaccine development
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Date
2013Author
Ojwang, Awino Maureiq Edith
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Melanoma antigens (MAGE) are imrnunogcns expressed ill malignancies but silenced III
somatic tissues except testis. They are grouped into ten subfamilies and at least one subfamily is
expressed ill a cancer type. In vaccinology, their tumor specific expression eliminates
autoimmunity, antitumor effects arrests tumorigenesis and epitopes promiscuity matches human
leukocyte antigen polymorphism. MAGE based vaccines in clinical trials are limited to
subfamilies and target single tumors. Many epitopes have been reported but an analysis or
universal epitopes that cut across all subfamilies has never been investigated. This in silico study
was focused on finding conserved epitopes within the subfamilies, A conserved motif analysis of
all proteornes was done using ClustalO, Jalview and Cyto scape tools. There was a notable
absence of strong conservation explained as a consequence of weak functional constraints during
gene evolution. An analysis of the antigens' extracellular topology was achieved using TMI IMM
server and all antigens except MAGE 11I were found to be extracellular. 13 and T cell cpitopes
within the extracellular conserved motifs were then identified via a pipeline ofpredietive servers
(BCPreds, IEOB, ProPred 1 and Il, MHCPred and T-epitope designer) and tested for antigenicity
using VaxiJen server. For results, 20 antigenic 13 cell epitopes (18-20 mer) and> lOT cell
epitopes (8-15 mer) binding to human leukocyt.e antigen alleles; HLA-A*020 I, -A*0204, -
13*2705, -ORB I *0 101, and -DRB 1*040 I, are given. 8-mer T cell epitopes were found to be the
most conserved and are thus considered universal epitopes. However, other epitopes (9-15 Iller)
are only conserved wit.hin subfamilies hence strings of epitopes were formed to get universal
polytopes. These findings will inform the design of a multivalent universal MAGE vaccine that
targets more than nineteen tumors. This pipeline confirms six reported epitopes (from in vitro
studies) thus showing the efficacy or using in silica tools in epitope prediction.
Citation
Master of Science degree in Bioinformatics,Publisher
University of Nairobi,