In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.

Preksha Shah, Jaymisha Mistry, Pedro A Reche, Derek Gatherer, Darren R Flower

Journal: Molecular immunology 2019;97():56-62

PMID: 29567319

Full Text on Elsevier Science View on PubMed

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.

Address: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.; Immunomedicine Group, Facultad de Medicina, Departamento de Inmunologia & O2, Universidad Complutense de Madrid, Madrid, Spain.; Division of Biomedical & Life Sciences, Faculty of Health & Medicine, Lancaster University, Lancaster LA1 4YW, UK.; School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK. Electronic address: [email protected].

DOI: 10.1016/j.molimm.2018.03.007

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MeSH Terms: Amino Acid Sequence, BCG Vaccine, Computational Biology, Computer Simulation, Drug Design, Epitope Mapping, Epitopes, Humans, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis Vaccines