Identification of Vaccine Candidates Against Staphylococcus Aureus: An in Silico Reverse Vaccinology Approach
CitationSharma, Shekhar. 2019. Identification of Vaccine Candidates Against Staphylococcus Aureus: An in Silico Reverse Vaccinology Approach. Master's thesis, Harvard Extension School.
AbstractThe goal of this research was to identify novel antigenic protein targets for designing a vaccine against Staphylococcus aureus. S. aureus is both a commensal bacterium and a human pathogen. It asymptomatically colonizes the epithelium of 25-50% of the population. The factors that make a benign patch of S. aureus virulent are not well understood. However, the event is often preceded by an increase in coagulase secretion. Bacteremia and endocarditis are the serious outcomes of an S. aureus infection. Presently, there is no vaccine for the pathogen though SA4Ag, under development, is promising. In this in silico experiment, 330 candidate proteins were identified using the principles of reverse vaccinology which uses genomic data for computing the antigenic targets. Custom developed computer code and online bioinformatics tools were used to conduct this experiment. 14,322 whole genome sequences (WGSs) of S. aureus were downloaded from GenBank and allied datacenters. The data was curated for completeness and diversity. 6,538 ORFs were extracted from the WGSs using biostatistical algorithms. The ORFs were translated into proteins. In parallel, 1,574 genes were extracted from the WGSs using bioinformatics tools. The location of ORFs were matched with that of known genes. The proteins translated from ORFs were compared with the co-located genes to verify the ORF detection algorithm and identify potential unknown genes. Based on the probability that a protein translated from an ORF might translocate to the cell surface, 1,045 candidate proteins were chosen. Finally, 330 proteins were identified that could be candidates for designing a vaccine against S. aureus. The results supported the objective of this research, namely, to find antigenic proteins expressed by S. aureus. The identified proteins must be validated in vitro. The future studies could include investigating ORFs in the context of the whole genome, IL-17 and coagulase pathways and membrane bound lipoproteins and glycoproteins.
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