©1996-2019. All Rights Reserved. Online
Journal of Bioinformatics . You
may not store these pages in any form except for your own personal use. All
other usage or distribution is illegal under international copyright treaties.
Permission to use any of these pages in any other way besides the before mentioned
must be gained in writing from the publisher. This article is exclusively
copyrighted in its entirety to OJB publications. This article may be copied
once but may not be, reproduced or re-transmitted
without the express permission of the editors. This
journal satisfies the refereeing requirements (DEST) for the Higher Education
Research Data Collection (Australia). Linking: To link to this page or any pages linking
to this page you must link directly to this page only here rather than put up
your own page.
OJBTM
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
ABSTRACT
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).
FULL-TEXT (SUBSCRIBE OR PURCHASE
TITLE $25USD)