Design and Validation of a Polyunit Epitope Vaccine Against <i>Enterococcus faecium</i>

Enterococcus faecium has developed resistance to multiple antibiotics, worsening the global health crisis. In this research study, immunoinformatics and biophysics approaches were applied to predict novel epitopes in the core proteins E. faecium. Bacterial pan-genome analysis predicted 4886 proteins as part of the core proteome. In the core proteins, seven proteins were found in extracellular region. In seven extracellular portions, three proteins were found to be virulent. In virulent proteins, one protein was predicted as an allergen and two proteins were nonallergens. Based on subtractive proteomics, two extracellular and probable antigenic proteins (glucosaminidase domain-containing protein and N-acetylmuramoyl-L-alanine amidase) were selected for epitopes prediction analysis. In epitope prediction, six [Formula: see text]-cell novel epitopes of different lengths were predicted from each selected protein. Next immunoinformatics filters were utilized to assess immunoinformatics properties of vaccine construct, and eight novel epitopes SARHHRPKR, RHHRPKRKM, HADEQGSQTV, PQHVHADEQ, RFDTPSTGSA, STSSSSTTDV, SSSSTTDVN and KVSLETKEF have opted for epitope-based vaccine construction. The selected epitopes were connected through GPGPG linkers and coupled with the adjuvant through the EAAAK linker to design multi-epitopes vaccine construct. The 3D structure of the vaccine was modeled and used in interaction analysis. The interaction analysis revealed the best dock conformation with targeted immune receptors. Furthermore, through biophysics studies, the intermolecular binding mode of vaccine receptors was reported to be dynamically stable in 500 nanoseconds. Next, the C-ImmSim server predicted that the model vaccine could induce strong immunological responses against E. faecium. The study outcomes predicted the effectiveness of a multi-epitope-based vaccine as a promising therapeutic approach for E. faecium.