Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Mol Immunol. 2014 Sep;61(1):16-22. doi: 10.1016/j.molimm.2014.04.009. Epub 2014 May 20.
Epitope-based vaccines permit the selection of only a specific subset of epitopes to induce the necessary immune response, thus providing a rational alternative to conventional design approaches. Using a range of immunoinformatics tools, we identified a novel, contiguous 28 amino acid multi-epitope cluster within the highly conserved secretory protein Ag85B of Mycobacterium tuberculosis, the causative agent of TB. This cluster, named Ep85B, is composed of epitopes which bind to three HLA Class I and 15 Class II molecules, and harbors the potential to generate 99% population coverage in TB-endemic regions. We experimentally evaluated the capacity of Ep85B to elicit T-cell immune responses using whole blood cells and, as predicted, observed significant increases in populations of both CD4+ and memory CD4+ CD45RO+ T-cells. Our results demonstrate the practical utility of an epitope-based design methodology - a strategy that, following further evaluation, may serve as an additional tool for the development of novel vaccine candidates against TB and other diseases.
基于表位的疫苗只能选择特定的表位亚群来诱导必要的免疫反应,因此为传统设计方法提供了合理的替代方案。我们使用一系列免疫信息学工具,在结核分枝杆菌(导致结核病的病原体)高度保守的分泌蛋白 Ag85B 内鉴定了一个新的、连续的 28 个氨基酸的多表位簇。这个簇名为 Ep85B,由与三种 HLA Ⅰ类和 15 种 HLA Ⅱ类分子结合的表位组成,具有在结核病流行地区产生 99%人群覆盖率的潜力。我们使用全血细胞实验评估了 Ep85B 引发 T 细胞免疫反应的能力,正如预测的那样,观察到 CD4+和记忆 CD4+ CD45RO+T 细胞群体显著增加。我们的结果证明了基于表位的设计方法的实际效用——这种策略在进一步评估后,可能成为开发针对结核病和其他疾病的新型候选疫苗的另一种工具。