Designing multiepitope subunit vaccine for Mycobacterium tuberculosis: Immunoinformatic approach

Abstract

Background: Tuberculosis is the most common cause of death among adults in the most economically age groups and immunecompromised patients. Increase in transmission of Mycobacterium tuberculosis strains with drug resistance has complicated tuberculosis control and continue to pose a challenge to global public health. Mycobacterium tuberculosis has recently proved to stimulate strong humoral immunity against adhesin such as hsp70. Vaccination is an effective means of protection and prevention of spread of vaccinable preventable diseases. Bacillus Calmette–Guérin vaccine is the currently the only vaccine used to protect against tuberculosis, hence the need to design more effective vaccines that will protect adults and immunocompromised patients. Methods and materials: Proteins used in this study were retrieved from the NCBI database. The tools used for the design of the vaccine include AntigenPro server for antigenicity prediction, NETCTL server for CTL epitopes, and IEDB server for HTL epitopes. AAY and GPGPG were used to link both suitable CTL and HTL epitopes respectively while EAAK was used as adjuvants. Protparam server was used to compute the physiochemical parameters of vaccine construct. Allergenicity was predicted using Allertop v2.0. Vaccine 3D model and tertiary structure was predicted using RaptorX server and later refined using the Galaxyrefine server. Results: The proteins used for the vaccine construct were found to be antigenic as predicted by ANTIGENpro having a score of ≥0.8. A final vaccine construct of 447 amino acids residues was designed using 20 CTL and 10 HTL epitopes. The allergenicity test showed the vaccine protein is non-allergenic in nature and safe for human use. The instability index and aliphatic index were given to be 27.76 and 83.53 respectively which classifies the protein to be thermostable. The estimated half life in mammalian reticulocytes was given as 4.4 h in-vitro. Conclusion: The designed vaccine construct is stable, immunogenic with high antigenic properties, non allergenic in nature and safe for human use. Designing multiepitope subunit vaccine using Immunoinformatics approach shows that it is feasible to produce effective vaccines against tuberculosis and save millions of lives from being lost every year.