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结核分枝杆菌表位组合疫苗的计算机设计。

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.

机构信息

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.

出版信息

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.

摘要

有效控制结核分枝杆菌是全球的必要之举。2015 年,结核病(TB)导致的死亡人数超过了艾滋病。鉴于结核分枝杆菌多药耐药形式的日益流行,对有效结核病疫苗的需求变得至关重要。目前,唯一获得许可的结核病疫苗是卡介苗(BCG)。然而,BCG 有许多缺点,限制了其效力和适用性。我们应用先进的计算程序来开发一种通用的结核病疫苗和一种针对东非的疫苗。我们的方法选择了一组最佳的高度保守、经过实验验证的表位,具有高预期人群覆盖率(PPC)。通过严格的数据分析,我们选择了五种不同的潜在疫苗组合,每个组合在东非的 PPC 都超过 80%,在世界范围内的 PPC 都超过 90%。两种潜在的疫苗仅包含 CD8+表位,而其他疫苗则包含 CD4+和 CD8+表位。我们的主要候选疫苗是一个由七个表位组成的假设组合:SRGWSLIKSVRLGNA、KPRIITLTMNPALDI、AAHKGLMNIALAISA、FPAGGSTGSL、MLLAVTVSL、QSSFYSDW 和 KMRCGAPRY,具有 97.4%的全球 PPC 和 92.7%的东非 PPC。

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