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Online Journal of Bioinformatics ©
Volume 15 (1): 114-132, 2014.
In silico identification of universal HLA stimulating B and T-cell restricted mage epitopes for vaccine development.
Awino Maureiq Edith Ojwang1, Daniel A Achinko PhD2, Anton Dormer MD MS3, Robinson Musembi, PhD4,
Walter Mwanda, MD, PhD5, James Ochanda, PhD6.
1Centre for Biotechnology and Bioinformatics (CEBIB), University of Nairobi, 2International Center of Insect Physiology and oncology (ICIPE), Nairobi, Kenya, PepVax, Inc.10411 Motor City Drive, Suite #750, Bethesda, MD 20817, USA, 3PepVax, Inc. 10411 Motor City Drive, Suite #750, Bethesda, MD 20817, USA, 4Department of Physics, University of Nairobi, 5nstitute for Tropical and Infectious diseases (UNITID) University of Nairobi, 6Centre for Biotechnology and Bioinformatics (CEBIB), University of Nairobi, P.O Box 30197, G.P.O, Nairobi, Kenya
Edith Ojwang AM, Achinko DA2, Dormer A, Musembi R, Mwanda W, Ochanda J., In silico identification of universal HLA stimulating B and T-cell restricted mage epitopes for vaccine development, Onl J Bioinform., 15 (1): 114-132, 2014. Melanoma antigens are immunogens expressed in various malignancies but silenced in somatic tissues. They are grouped into ten subfamilies and at least one subfamily is expressed in a cancer type. Given the specificity of in silico epitope targets previously used in vaccine technology against MAGE protein family, peptide length, epitope conservation and HLA allele diversity studies have not been performed. This in silico study is the first focusing on conserved epitopes design across HLA alleles for the MAGE proteins family with aim to analyze domain distribution and conservation through ClustalO, Jalview 2.7 and Cytoscape 2.8.3 routine stand alone software, analyze protein sequence topology through TMHMM server 2.0 and identify universal B and T cell epitopes via a pipeline of predictive servers (BCPREDS, IEDB, ProPred-I, ProPred, MHCPred 2.0 and T-EPITOPE designer) and tested for antigenicity using VaxiJen 2.0 server. There was a notable absence of strong MAGE Homology Domain conservation which could be explained as a consequence of weak functional constraints during gene evolution. Twenty predicted antigenic B cell epitopes (18-20-mers) from individual sub families derived >10 T cell epitopes (8-15-mers) binding to human leukocyte antigen alleles; HLA-A*0201, -A*0204, -B*2705, -DRB1*0101, and -DRB1*0401. Eight and nine monomer T cell epitopes were found to be the most conserved with 9 monomers having the highest coverage for HLA allele types and different MAGE protein subclasses thus making them universal epitopes for MAGE Proteins. However, other epitopes (10-15-mers) are only conserved within subclasses. These findings will inform the design of a multivalent universal MAGE vaccine that targets many tumors. Our pipeline confirms some reported epitopes (from in vitro studies) thus showing the efficacy of using in silico tools in epitope prediction
Keywords: Melanoma antigen, Cancer, In silico, B-cell epitope, T-cell epitope, Human Leukocyte Antigen (HLA).