In silico development of a broad-spectrum vaccine against ESKAPE pathogens

Area of Science:

• Microbiology
• Immunology
• Computational Biology

Background:

• Antimicrobial-resistant ESKAPE pathogens pose a significant global health threat, limiting treatment options for critical infections.
• Vaccination offers a crucial preventive strategy against bacterial infections, including those caused by antibiotic-resistant strains.

Purpose of the Study:

• To design a novel epitope-based vaccine targeting conserved antigens across the ESKAPE pathogens.
• To computationally evaluate the vaccine construct's immunogenicity and potential efficacy.

Main Methods:

• Pangenome analysis of ESKAPE pathogens to identify core proteomes and antigenic proteins (porins OmpA, OprD, TolC; adhesins Acm, Cna).
• Reverse vaccinology to predict and select immunogenic, non-allergenic, and non-toxic T-cell and B-cell epitopes.
• In silico construction of a vaccine incorporating epitopes, adjuvant RS09, and linkers, followed by molecular docking and dynamics simulations.

Main Results:

• Identified conserved antigenic proteins and selected optimal epitopes based on physicochemical properties, antigenicity, and HLA binding.
• Molecular simulations confirmed stable interactions between the vaccine construct and immune system receptors.
• In silico immune simulations predicted the induction of both humoral and cell-mediated immune responses.

Conclusions:

• The designed epitope-based vaccine construct shows potential as an effective and safe candidate for preventing infections caused by ESKAPE pathogens.
• This computational approach offers a promising strategy for developing vaccines against multidrug-resistant bacteria.