PDF(Pubmed)
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，可能导致严重的疾病，包括盆腔炎，异位妊娠,和输卵管性不孕症如果不治疗。目前的战略,包括筛查和抗生素，由于无症状病例率高和后勤挑战，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。免疫信息学分析用于设计多表位衣原体疫苗抗原。预测并选择来自五种高度保守和免疫原性Ct抗原的B-和T-细胞表位用于疫苗设计。最后的结构，用霍乱毒素A1亚基（CTA1）佐剂，进一步筛选免疫原性。CTA1-MECA被鉴定为抗原性和非变应原性。预测了三级结构，精致,并验证为良好的质量模型。分子对接在疫苗和toll样受体4（TLR4）之间表现出强烈的相互作用。此外,与保护一致的免疫反应，包括IFN-γ，IgG+IgM抗体，在免疫模拟中预测接种后的T细胞和B细胞反应。在大肠杆菌表达载体中表达构建体证明是有效的。为了进一步验证疫苗的有效性，我们评估了其在小鼠中的免疫原性。用CTA1-MECA免疫在粘膜和全身区室中引起高水平的衣原体特异性抗体。
