Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium

Abstract

Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.

Designing multi-epitope-based vaccine targeting surface immunogenic protein of Streptococcus agalactiae using immunoinformatics to control mastitis in dairy cattle

“…In silico restriction cloning was carried out using the pET28( +) vector for easy purification and the manufacture of prospective candidate vaccines on a larger scale [57]. However, based on the immune simulation study, we can conclude that vaccines are effective at eliciting the immune response [42][43][44]. One of the criteria for being a successful vaccine candidate is the induction of B-cells and T-cells [63][64][65].…”

“…Therefore, the entire simulation ran for 1050 simulation steps during the course of three consecutive injections with time steps of 1, 84, and 168 (Where 1-time steps = 8 h). The default settings for the other simulation parameters were used [42][43][44].…”

Contriving multi-epitope vaccine ensemble for monkeypox disease using an immunoinformatics approach

“…The sequence’s antigenicity prediction is essential because it reveals whether the epitope sequence is likely to be recognized by immunogenic cells in the human body. Another significant barrier to vaccine development is the possibility of allergenicity, which occurs when numerous vaccines drive the immune system into an allergic response ( 71 ). Thus, herein, we chose epitopes predicted to be highly antigenic and did not show allergenic potential for the host immune system.…”

Vancomycin Resistance in Enterococcus and Staphylococcus aureus

“…Antisera raised to enterococcal polysaccharides have been shown to promote opsonic killing in vitro and protect against enterococcal bacteremia in vivo , while vaccination with recombinant enterococcal virulence factors and antigens also proved to be opsonic in vitro and promoted bacterial clearance in mice [ 618 ]. Multi-epitope vaccines [ 619 ] and conjugated vaccines [ 620 , 621 ] have also demonstrated promising results. However, there are currently no Enterococcus vaccines in development, and none have been approved for clinical use [ 616 , 619 ].…”

“…Multi-epitope vaccines [ 619 ] and conjugated vaccines [ 620 , 621 ] have also demonstrated promising results. However, there are currently no Enterococcus vaccines in development, and none have been approved for clinical use [ 616 , 619 ].…”