Pan genome based reverse vaccinology approach to explore Enterococcus faecium (VRE) strains for identification of novel multi-epitopes vaccine candidate

Abstract

Enterococcus faecium is regarded as fourth most emerging common pathogen causing hospital acquired infections (HAIs), with high mortality rate, especially in children, elderly and immunocompromised patients. Recently, due to the emergence of E. faecium resistant strains especially vancomycin resistance (VRE) and their continuously growing resistivity to antibiotics, design of safe vaccine remains a choice for its control. Alternative control through vaccination has received much attention, but there is no clinically approved vaccine against this pathogen. Therefore, in current study we have applied a triple helix approach i.e., Pan-genome, subtractive genome and reverse vaccinology to identify and design potential vaccine candidates and multiepitope-based vaccine (MEV) construct against E. faecium (via core genome analysis from 216 strains). In this study, only 2 outer membrane proteins were identified through genome subtraction of resistant strains genes against human and essential proteins. Subsequently, phosphate ABC transporter substrate binding protein (Psts) was selected as a promiscuous vaccine candidate to develop a potent vaccine model. A final of four epitopes from CD8 + T-cell, CD4 + T-cell epitopes, and B-cell were shortlisted from outer membrane protein with highly antigenic, IFN-γ inducer, and overlapping characteristics for the construction of twelve vaccine models. The V3 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic and most stable in terms of molecular docking and simulation studies against six HLAs, TLR2, and TLR4 complex. So far, this protein and multiepitope have never been characterized as vaccine targets against E. faecium. The current study proposed V3 as a significant vaccine candidate that could help the scientific community to treat E. faecium infections.

Keywords: Chimeric vaccine model; Enterococcus faecium; Multiepitope; Pangenome analysis; Phosphate ABC transporter substrate binding protein (Psts); Reverse vaccinology.