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基于免疫信息学方法探索幽门螺杆菌的全免疫表位设计和开发多表位嵌合疫苗。

Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach.

机构信息

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh, Mandi, 175005, India.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177, Stockholm, Sweden.

出版信息

BMC Bioinformatics. 2023 Sep 22;24(1):358. doi: 10.1186/s12859-023-05454-2.

Abstract

BACKGROUND

Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection.

RESULTS

We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector.

CONCLUSION

The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world's population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

摘要

背景

幽门螺杆菌是导致胃溃疡、胃腺癌和胃淋巴瘤的主要病原体,被世界卫生组织列为 1 类致癌物。质子泵抑制剂和抗生素联合治疗幽门螺杆菌虽然有效,但也导致了抗生素耐药性增加、患者不满和再次感染的机会。因此,有效的疫苗仍然是针对这种感染进行大规模人群预防的最适合的选择。

结果

我们通过筛选其分泌/外膜蛋白,对幽门螺杆菌的多嵌合亚单位疫苗候选物进行了建模。我们在这些蛋白中鉴定出了 B 细胞、MHC-II 和 IFN-γ 诱导表位。使用不同的计算工具评估了人群覆盖率、抗原性、物理化学性质和二级结构,结果表明它可以成为一种良好且有效的疫苗候选物。对 3-D 结构进行了预测、优化、验证,并与 TLR 进行了对接。最后,我们进行了分子对接/模拟和免疫模拟研究,以验证相互作用的稳定性,并在计算机上克隆了表位序列到 pET28b(+)质粒载体中。

结论

多表位构建的疫苗包含 T 细胞、B 细胞以及 IFN-γ 诱导表位,具有产生良好细胞介导免疫和体液反应的特性。这种疫苗可以保护世界上大多数人口。对接研究和免疫模拟分别显示出与 TLRs 以及细胞介导和体液免疫反应的良好结合。总的来说,我们试图设计一种多表位疫苗,并期望这种疫苗在体内使用时能对幽门螺杆菌感染显示出令人鼓舞的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82a/10517479/5aa3a987e74b/12859_2023_5454_Fig1_HTML.jpg

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