In silico design and evaluation of a multiepitope vaccine against Bordetella pertussis: structural, immunological, and biological properties

Despite widespread vaccination, the increasing incidence of pertussis underscores the urgent need for innovative vaccine strategies. This study aims to design and analyze, using in silico methods, a multiepitope protein that incorporates epitopes from the S1 subunit of pertussis toxin and the type 1 immunodominant domain of filamentous hemagglutinin (F1). The goal is to enhance both systemic and mucosal immunity through the incorporation of the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE).

Using reverse vaccinology, we predicted immunogenic epitopes for lymphocytes derived from the S1 and F1 proteins. The epitopes were assembled into a multiepitope construct named mF1S1-C-CPE, which was then evaluated for its physicochemical, immunological, and biological properties. Immunoinformatics tools were employed to analyze antigenicity, allergenicity, and population coverage. Additionally, molecular docking simulations of peptide‒MHC and mF1S1-C-CPE_TLR2/TLR4 binding were conducted.

Structural analysis indicated that the final multiepitope construct maintained stability and solubility in aqueous environments. Immunoinformatic analysis revealed strong immunogenic properties, effectively eliciting both systemic and mucosal immune responses. Molecular docking demonstrated high-affinity binding patterns between the peptides (both individual or within the mF1S1-C-CPE) and corresponding HLA molecules. Additionally, molecular docking simulations of mF1S1-C-CPE and TLR2/TLR4 indicated strong binding affinity to receptors of innate immunity. The construct was predicted to be stable, soluble, and suitable for expression in Escherichia coli (CAI 0.93; GC content 54.9%).

This innovative approach holds promise for enhancing pertussis vaccination strategies by improving mucosal immune responses. Further in vivo studies are essential to validate the efficacy of this multiepitope vaccine candidate.