Suppr超能文献

针对衣原体的多表位疫苗的计算机设计与分析。

In silico design and analysis of a multiepitope vaccine against Chlamydia.

机构信息

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine. 720 Westview Drive, Atlanta, GA 30310, United States.

出版信息

Pathog Dis. 2024 Feb 7;82. doi: 10.1093/femspd/ftae015.

Abstract

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial infection worldwide, potentially leading to severe pathologies including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility if left untreated. Current strategies, including screening and antibiotics, have limited effectiveness due to high rates of asymptomatic cases and logistical challenges. A multiepitope prophylactic vaccine could afford long-term protection against infection. Immunoinformatic analyses were employed to design a multiepitope Chlamydia vaccine antigen. B- and T-cell epitopes from five highly conserved and immunogenic Ct antigens were predicted and selected for the vaccine design. The final construct, adjuvanted with cholera toxin A1 subunit (CTA1), was further screened for immunogenicity. CTA1-MECA (multiepitope Chlamydia trachomatis antigen) was identified as antigenic and nonallergenic. A tertiary structure was predicted, refined, and validated as a good quality model. Molecular docking exhibited strong interactions between the vaccine and toll-like receptor 4 (TLR4). Additionally, immune responses consistent with protection including IFN-γ, IgG + IgM antibodies, and T- and B-cell responses were predicted following vaccination in an immune simulation. Expression of the construct in an Escherichia coli expression vector proved efficient. To further validate the vaccine efficacy, we assessed its immunogenicity in mice. Immunization with CTA1-MECA elicited high levels of Chlamydia-specific antibodies in mucosal and systemic compartments.

摘要

沙眼衣原体(Ct)是全球最常见的性传播细菌感染,如果不治疗,可能导致盆腔炎、宫外孕和输卵管不孕等严重疾病。目前的策略,包括筛查和抗生素,由于无症状病例的高发病率和后勤挑战,效果有限。多表位预防性疫苗可以提供针对感染的长期保护。免疫信息学分析被用于设计一种多表位沙眼衣原体疫苗抗原。从五种高度保守和免疫原性的 Ct 抗原中预测和选择 B 细胞和 T 细胞表位用于疫苗设计。最后构建体,用霍乱毒素 A1 亚单位(CTA1)佐剂,进一步筛选免疫原性。CTA1-MECA(多表位沙眼衣原体抗原)被鉴定为具有抗原性和非变应原性。预测、精制和验证了三级结构作为一种高质量模型。分子对接显示疫苗与 Toll 样受体 4(TLR4)之间存在强烈相互作用。此外,在免疫模拟中预测了接种疫苗后与保护一致的免疫反应,包括 IFN-γ、IgG+IgM 抗体以及 T 和 B 细胞反应。在大肠杆菌表达载体中表达该构建体证明是有效的。为了进一步验证疫苗的疗效,我们在小鼠中评估了其免疫原性。用 CTA1-MECA 免疫可在粘膜和全身部位诱导高水平的沙眼衣原体特异性抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e92a/11234648/c024b905e059/ftae015fig1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验