In silico design of Mycobacterium tuberculosis epitope ensemble vaccines

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.

Publication DOI: https://doi.org/10.1016/j.molimm.2018.03.007
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International. Funding: BIO2014:54164-R; Inmunotek S.L.
Uncontrolled Keywords: Tuberculosis,Vaccine,Immunoinformatics
Publication ISSN: 1872-9142
Full Text Link:
Related URLs: https://www.sci ... 161589018300580 (Publisher URL)
PURE Output Type: Article
Published Date: 2018-05
Published Online Date: 2018-03-19
Accepted Date: 2018-03-10
Authors: Shah, Preksha
Mistry, Jaymisha
Reche, Pedro A.
Gatherer, Derek
Flower, Darren R (ORCID Profile 0000-0002-8542-7067)

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