SCREENING FOR PUTATIVE VACCINE CANDIDATES OF Onchocerca volvulus USING GENOMIC AND PROTEOMIC ANALYSES
SCREENING FOR PUTATIVE VACCINE CANDIDATES OF Onchocerca volvulus USING GENOMIC AND PROTEOMIC ANALYSES
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Date
2018-07
Authors
SHEYIN, Abraham
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Abstract
Onchocerca volvulus, a parasitic worm, is the causative agent of onchocerciasis (river blindness) which is transmitted by blackflies of the genus Simulium to humans. It is a neglected tropical disease affecting more than 37 million people worldwide. Nigeria accounts for about 40 percent of the global Onchocerciasis burden and is the most endemic country in the world. There is no vaccine yet for the prevention of the disease. Treatment is done by administering Ivermectin that kills only the microfilaria, but does not kill the adult worm. The danger of resistance to this drug has been reported in Ghana. The development of a vaccine would help solve these challenges. In this study, reverse vaccinology, was used to screen the genome and proteome of O. volvulus using bioinformatics tools so as to find proteins of the pathogen that can serve as vaccine candidates. From 6259 proteins of O. volvulus in the Uniprot database 4551 uncharacterized protein sequences were collected. Using Subtractive Genomics Approach, NCBI tblastn program was used to screen out sequences similar to humans, to avoid the occurrence of autoimmunity. Hence, 793 uncharacterized protein sequences that are non-orthologues to humans were identified. From these sequences, signal peptides were predicted using the Linux programs: TargetP, SignalP and Phobius. Transmembrane helices were also predicted using the Linux programs: TMHMM and Phobius. As a result, 22 putative proteins containing both signal peptides and a single transmembrane helice (literature shows that the more the helices in a protein the less the correctness of prediction) were subjected to Major Histocompatibility Complex (MHC) I and II peptide binding prediction and B-cell epitopes prediction. This was done using the Linux programs: Immune Epitope Database MHC I and II binding predictors and BepiPred respectively. Consequently, 133 epitopes were identified. Upon interpreting NCBI tblastn result, we suggest that four of the sequences function as components of the impervious cuticle of the pathogen. Furthermore, using comparative genomics via sequence similarity search approach, previously reported potential vaccine candidates of Dirofilaria immitis and Brugia malayi were compared with the genome of O. volvulus using the NCBI tblastn program. As a result, 1 more putative vaccine candidate - a characterized protein, was identified. This brings the number of putative vaccine sequences identified to 23. Experimental validation of these candidates is hereby recommended
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF MASTER OF SCIENCE DEGREE IN BIOTECHNOLOGY
DEPARTMENT OF BIOCHEMISTRY,
FACULTY OF SCIENCE,
AHMADU BELLO UNIVERSITY,
ZARIA, NIGERIA
Keywords
SCREENING,, PUTATIVE VACCINE,, CANDIDATES,, Onchocerca volvulus,, GENOMIC,, PROTEOMIC ANALYSES,