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新型结核疫苗候选物 HP13138PB 的生物信息学分析和一致性验证。

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB.

机构信息

Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, China.

Department of Geriatrics, The Eighth Medical Center of PLA General Hospital, Beijing, China.

出版信息

Front Immunol. 2023 Jan 27;14:1102578. doi: 10.3389/fimmu.2023.1102578. eCollection 2023.

DOI:10.3389/fimmu.2023.1102578
PMID:36825009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9942524/
Abstract

BACKGROUND

With the increasing incidence of tuberculosis (TB) and the shortcomings of existing TB vaccines to prevent TB in adults, new TB vaccines need to be developed to address the complex TB epidemic.

METHOD

The dominant epitopes were screened from antigens to construct a novel epitope vaccine termed HP13138PB. The immune properties, structure, and function of HP13138PB were predicted and analyzed with bioinformatics and immunoinformatics. Then, the immune responses induced by the HP13138PB were confirmed by enzyme-linked immunospot assay (ELISPOT) and Th1/Th2/Th17 multi-cytokine detection kit.

RESULT

The HP13138PB vaccine consisted of 13 helper T lymphocytes (HTL) epitopes, 13 cytotoxic T lymphocytes (CTL) epitopes, and 8 B-cell epitopes. It was found that the antigenicity, immunogenicity, and solubility index of the HP13138PB vaccine were 0.87, 2.79, and 0.55, respectively. The secondary structure prediction indicated that the HP13138PB vaccine had 31% of α-helix, 11% of β-strand, and 56% of coil. The tertiary structure analysis suggested that the Z-score and the Favored region of the HP13138PB vaccine were -4.47 88.22%, respectively. Furthermore, the binding energies of the HP13138PB to toll-like receptor 2 (TLR2) was -1224.7 kcal/mol. The immunoinformatics and real-world experiments showed that the HP13138PB vaccine could induce an innate and adaptive immune response characterized by significantly higher levels of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10.

CONCLUSION

The HP13138PB is a potential vaccine candidate to prevent TB, and this study preliminarily evaluated the ability of the HP13138PB to generate an immune response, providing a precursor target for developing TB vaccines.

摘要

背景

随着结核病(TB)发病率的增加和现有 TB 疫苗在成人中的预防效果存在缺陷,需要开发新的 TB 疫苗来应对复杂的 TB 流行。

方法

从抗原中筛选优势表位构建新型表位疫苗,命名为 HP13138PB。利用生物信息学和免疫信息学预测和分析 HP13138PB 的免疫特性、结构和功能。然后,通过酶联免疫斑点(ELISPOT)和 Th1/Th2/Th17 多细胞因子检测试剂盒确认 HP13138PB 诱导的免疫反应。

结果

HP13138PB 疫苗由 13 个辅助 T 淋巴细胞(HTL)表位、13 个细胞毒性 T 淋巴细胞(CTL)表位和 8 个 B 细胞表位组成。发现 HP13138PB 疫苗的抗原性、免疫原性和可溶性指数分别为 0.87、2.79 和 0.55。二级结构预测表明,HP13138PB 疫苗有 31%的α-螺旋、11%的β-折叠和 56%的无规卷曲。三级结构分析表明,HP13138PB 的 Z 分数和 Favored 区分别为-4.47和 88.22%。此外,HP13138PB 与 Toll 样受体 2(TLR2)的结合能为-1224.7 kcal/mol。免疫信息学和真实世界实验表明,HP13138PB 疫苗可诱导以干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)和 IL-10 等细胞因子水平显著升高为特征的固有和适应性免疫反应。

结论

HP13138PB 是一种有潜力的预防 TB 的疫苗候选物,本研究初步评估了 HP13138PB 产生免疫反应的能力,为开发 TB 疫苗提供了前体靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/69e6beff19f9/fimmu-14-1102578-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/f36a7cfcb85d/fimmu-14-1102578-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/5fd933c65066/fimmu-14-1102578-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/83d8dd1c07d5/fimmu-14-1102578-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/f9d4b5cd253e/fimmu-14-1102578-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/70995218c532/fimmu-14-1102578-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/a045d3015a3b/fimmu-14-1102578-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/cc6ee42bc8c4/fimmu-14-1102578-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/01f7b34db874/fimmu-14-1102578-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/69e6beff19f9/fimmu-14-1102578-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/f36a7cfcb85d/fimmu-14-1102578-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/eb6705b09eab/fimmu-14-1102578-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/ccf2058e6b4e/fimmu-14-1102578-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/5fd933c65066/fimmu-14-1102578-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/83d8dd1c07d5/fimmu-14-1102578-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/f9d4b5cd253e/fimmu-14-1102578-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/70995218c532/fimmu-14-1102578-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/a045d3015a3b/fimmu-14-1102578-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/cc6ee42bc8c4/fimmu-14-1102578-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/01f7b34db874/fimmu-14-1102578-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4547/9942524/69e6beff19f9/fimmu-14-1102578-g011.jpg

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