Tayhlor Tanner, F N U Medhavi, Shakyra Richardson, Yusuf O Omosun, Francis O Eko
{"title":"针对衣原体的多表位疫苗的硅学设计和分析。","authors":"Tayhlor Tanner, F N U Medhavi, Shakyra Richardson, Yusuf O Omosun, Francis O Eko","doi":"10.1093/femspd/ftae015","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234648/pdf/","citationCount":"0","resultStr":"{\"title\":\"In silico design and analysis of a multiepitope vaccine against Chlamydia.\",\"authors\":\"Tayhlor Tanner, F N U Medhavi, Shakyra Richardson, Yusuf O Omosun, Francis O Eko\",\"doi\":\"10.1093/femspd/ftae015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":19795,\"journal\":{\"name\":\"Pathogens and disease\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-02-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234648/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pathogens and disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/femspd/ftae015\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathogens and disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/femspd/ftae015","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
沙眼衣原体(Ct)是全球最常见的性传播细菌感染,如果不及时治疗,有可能导致严重的病变,包括盆腔炎、宫外孕和输卵管性不孕。目前的策略包括筛查和抗生素,但由于无症状病例比例高和后勤方面的挑战,效果有限。多表位预防性疫苗可为预防感染提供长期保护。免疫形式分析被用来设计多表位衣原体疫苗抗原。从五个高度保守且具有免疫原性的 Ct 抗原中预测并选择了 B 细胞和 T 细胞表位用于疫苗设计。用霍乱毒素 A1 亚基(CTA1)佐剂的最终构建物进一步进行了免疫原性筛选。经鉴定,CTA1-MECA 具有抗原性和非过敏性。对三级结构进行了预测、完善和验证,认为这是一个优质模型。分子对接显示疫苗与类毒素受体 4(TLR4)之间有很强的相互作用。此外,在免疫模拟中预测了接种疫苗后与保护作用一致的免疫反应,包括 IFN-γ、IgG + IgM 抗体以及 T 细胞和 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功效,我们评估了小鼠的免疫原性。用 CTA1-MECA 进行免疫接种可在粘膜和全身产生高水平的衣原体特异性抗体。
In silico design and analysis of a multiepitope vaccine against Chlamydia.
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.
期刊介绍:
Pathogens and Disease publishes outstanding primary research on hypothesis- and discovery-driven studies on pathogens, host-pathogen interactions, host response to infection and their molecular and cellular correlates. It covers all pathogens – eukaryotes, prokaryotes, and viruses – and includes zoonotic pathogens and experimental translational applications.