In silico vaccine design for Yersinia enterocolitica: A comprehensive approach to enhanced immunogenicity, efficacy and protection

Abstract

Yersinia enterocolitica, a foodborne pathogen, has emerged as a significant public health concern due to its increased prevalence and multidrug resistance. This study employed reverse vaccinology to identify novel vaccine candidates against Y. enterocolitica through comprehensive in silico analyses. The core genome's conserved protein translocase subunit SecY was selected as the target, and potential B-cell, MHC class I, and MHC class II epitopes were mapped. 3B-cell epitopes, 3 MHCI and 11 MHCII epitopes were acquired. A multi-epitope vaccine construct was designed by incorporating the identified epitopes, TLR4 Agonist was used as adjuvants to enhance the immunogenic response. EAAAK, CPGPG and AYY linkers were used to form a vaccine construct, followed by extensive computational evaluations. The vaccine exhibited desirable physicochemical properties, stable secondary and tertiary structures as evaluated by PDBSum and trRosetta. Moreover, favorable interactions with the human Toll-like receptor 4 (TLR4) was observed by ClusPro. Population coverage analysis estimated the vaccine's applicability across 99.74 % in diverse populations. In addition, molecular dynamics simulations and normal mode analysis confirmed the vaccine's structural stability and dynamics in a simulated biological environment. Furthermore, codon optimization and in silico cloning facilitated the evaluation of the vaccine's expression potential in E. coli and pET-28a was used a recombinant plasmid. This study provides a promising foundation for the development of an efficacious vaccine against Y. enterocolitica infections.

Keywords: In silico analysis; Molecular docking; Multi-drug resistance; Multi-epitope vaccine; Reverse vaccinology; Yersinia enterocolitica; Yersiniosis.