Designing of a Novel Multi-Antigenic Epitope-Based Vaccine against E. hormaechei: An Intergraded Reverse Vaccinology and Immunoinformatics Approach.

Abstract

Enterobacter hormaechei is involved in multiple hospital-associated infections and is resistant to beta-lactam and tetracycline antibiotics. Due to emerging antibiotics resistance in E. hormaechei and lack of licensed vaccine availability, efforts are required to overcome the antibiotics crisis. In the current research study, a multi-epitope-based vaccine against E. hormaechei was designed using reverse vaccinology and immunoinformatic approaches. A total number of 50 strains were analyzed from which the core proteome was extracted. One extracellular (curlin minor subunit CsgB) and two periplasmic membrane proteins (flagellar basal-body rod protein (FlgF) and flagellar basal body P-ring protein (FlgI) were prioritized for B and T-cell epitope prediction. Only three filtered TPGKMDYTS, GADMTPGKM and RLSAESQAT epitopes were used when designing the vaccine construct. The epitopes were linked via GPGPG linkers and EAAAK linker-linked cholera toxin B-subunit adjuvant was used to enhance the immune stimulation efficacy of the vaccine. Docking studies of the vaccine construct with immune cell receptors revealed better interactions, vital for generating proper immune reactions. Docked complexes of vaccine with MHC-I, MHC-II and Tool-like receptor 4 (TLR-4) reported the lowest binding energy of −594.1 kcal/mol, −706.7 kcal/mol, −787.2 kcal/mol, respectively, and were further subjected to molecular dynamic simulations. Net binding free energy calculations also confirmed that the designed vaccine has a strong binding affinity for immune receptors and thus could be a good vaccine candidate for future experimental investigations.