Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Introduction: Rickettsia is vector-borne causing Rickettsial infections with high mortality. Currently, no vaccines are available for the prevention of rickettsioses. The study aims to identify B- and T- cell epitopes to peptides derived from TolC protein of rickettsial group of pathogens. Immunogenic linear B-cell epitopes and MHC class I and II T-cell epitopes predicted from the consensus sequences of TolC protein for each rickettsial species. The putative antigenic epitopes may trigger an effective immune response and prove to be a novel vaccine that protects against all rickettsial infections. Methods: MHC class-I binding T-cell epitopes were predicted along with TAP binding efficiency and proteasomal cleavage sites. Molecular docking study was carried out to investigate the binding affinity between the MHC-I protein molecules with the peptides. The MHC-peptide complex with the highest RMSD score was further used for molecular dynamic simulation study. Results: Three B-cell candidate peptide epitopes were selected, of which epitope IYPEGGAQYSRIRSAKNQTRNSA/VVQ is conserved across both typhus group and spotted fever group of rickettsial species was considered best suitable for candidate vaccine. The peptide epitope KLYEAKITR had a good RMSD score as well as promiscuous binding to 28 different HLA allele supertypes and was considered suitable for the development of subunit peptide vaccine. Conclusion: The B- and T- cell candidate peptide epitopes identified in our study would elicit B- and T-cell immune responses respectively and serve as a novel candidate peptide vaccine.