Development of peptide vaccine candidate using highly antigenic PE-PGRS family proteins to stimulate the host immune response against Mycobacterium tuberculosis H₃₇Rv: an immuno-informatics approach

Abstract

Tuberculosis (TB) is a fast spreading; transmissible disease caused by the Mycobacterium tuberculosis (M. tuberculosis). M. tuberculosis has a high death rate in its endemic regions due to a lack of appropriate treatment and preventative measures. We have used a vaccinomics strategy to create an effective multi-epitope vaccine against M. tuberculosis. The antigenic proteins with the highest antigenicity were utilised to predict cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes. CTL and HTL epitopes were covered in 99.97% of the population. Seven epitopes each of CTL, HTL, and LBL were ultimately selected and utilised to develop a multi-epitope vaccine. A vaccine design was developed by combining these epitopes with suitable linkers and LprG adjuvant. The vaccine chimera was revealed to be highly immunogenic, non-allergenic, and non-toxic. To ensure a better expression within the Escherichia coli K12 (E. coli K12) host system, codon adaptation and in silico cloning were accomplished. Following that, various validation studies were conducted, including molecular docking, molecular dynamics simulation, and immunological simulation, all of which indicated that the designed vaccine would be stable in the biological environment and effective against M. tuberculosis infection. The immune simulation revealed higher levels of T-cell and B-cell activity, which corresponded to the actual immune response. Exposure simulations were repeated several times, resulting in increased clonal selection and faster antigen clearance. These results suggest that, if proposed vaccine chimera would test both in-vitro and in-vivo, it could be a viable treatment and preventive strategy for TB.

Communicated by Ramaswamy H. Sarma

Keywords:

• Mycobacterium tuberculosis
• tuberculosis
• immunoinformatics
• multi-epitope vaccine
• dynamics simulation
• immune simulation

Disclosure statement

The authors declare no conflict of interest.

Funding

The authors acknowledge financial support from the Department of Science and Technology- SERB, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology under the research project GAP0145 (SERB-DST Grant no: EEQ/2016/000514).

Author contributions

AK conceptually did the work, writes the manuscript, PS helped in assisting the manuscript correctness, AA helped in MD simulation experiment and LSM helping in writing, correction and also handles all corresponding activities.

Data availability statement

Yes, the authors agreed for the availability of data to ensure data transparency norms.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Consent to participate

All authors participant agrees to publish this work in your esteem JBSD.

Consent to publish

Yes, all authors have given their consent.