Systems vaccinology for identification of new antigen(s) for designing a broad-spectrum epitope-based vaccine against Staphylococcus aureus

Abstract

Background: Staphylococcus aureus is one of the most versatile pathogens owing to its wide spectrum of infections in both humans and animals and notably powerful multi-drug resistance ability. Hence, it is an alarming global health threat, requires an urgent suitable therapeutic or prophylactic methods. Aim: The main target in this study was identification of vaccine candidates for designing a broad-spectrum multi-epitope domain-based vaccine. Methods: In this study, a systems vaccinology approach was exploited to construct a protein-protein interaction network for Staphylococcus aureus and identify hub proteins of this pathogen. All selected hub proteins were further shortlisted to be characterized in terms of gene ontology, key proteins in the pathogen-host interaction network, pathogenic clusters, virulence, antigenicity, genetic diversity, etc. to find potential vaccine candidates. Then vaccine target proteins were analyzed for their immunodominant B- and T-cell epitopes using multi-server or multi-algorithm based strategies. Finally, we have designed a self-amplifying mRNA vaccine construct that covers the largest number of overlapping epitopes to be produced and delivered through the gene-based approaches. Results: A protein-protein interaction network was conducted with 1832 proteins. With the aid of graph-theoretic based algorithms, 400 proteins were identified as hub proteins of this pathogen. In conclusion, 16 proteins were represented as potential vaccine candidates in which the final 3 candidates were chosen. Lastly, 8 domains containing several immunogenic epitopes of 3 proteins were used to design a multi-epitope domain-based vaccine construct. Conclusion: In this study, 3 proteins were presented as potential vaccine candidates and were developed to design a self-amplifying mRNA vaccine in a multi-antigen and multi-epitope domain-based platform.