In silico design of Mycobacterium tuberculosis epitope ensemble vaccines

Mol Immunol. 2018 May:97:56-62. doi: 10.1016/j.molimm.2018.03.007. Epub 2018 Mar 19.

Abstract

Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC.

Keywords: Immunoinformatics; Tuberculosis; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • BCG Vaccine / chemistry
  • BCG Vaccine / immunology
  • Computational Biology
  • Computer Simulation
  • Drug Design*
  • Epitope Mapping* / methods
  • Epitopes
  • Humans
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / chemical synthesis*
  • Tuberculosis Vaccines / chemistry
  • Tuberculosis Vaccines / immunology
  • Tuberculosis Vaccines / therapeutic use

Substances

  • BCG Vaccine
  • Epitopes
  • Tuberculosis Vaccines