Design of Epitopes from Treponema pallidum Lipoprotein Antigens for Syphilis Diagnosis and Treatment Prognosis.

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2025-06-13 Epub Date: 2025-05-23 DOI:10.1021/acsinfecdis.5c00155
Letícia Alves Borghezan, Lara Cândida de Sousa Machado, Iara Barreto Neves Oliveira, Mírian Ívens Fagundes, Nicoly Silveira Apolidório, Renato Canevari Dutra da Silva, Victor Garcia Freire, Antonio Augusto Schafer, Rahisa Scussel, Ricardo Andrez Machado-de-Ávila
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引用次数: 0

Abstract

Syphilis, a multistage sexually transmitted infection, causes severe complications if untreated. Accurate diagnosis remains difficult due to the low protein content of Treponema pallidum and in vitro culture difficulty. Advances in immunoproteomics have identified key antigens that enhance diagnostic accuracy. Epitopes of immunodominant antigen proteins Tp0171, Tp0435, Tp0574, Tp0684, and Tp0453 were designed by bioinformatics tools, and mimetic peptides were chemically synthesized. A diagnostic accuracy cross-sectional study was performed to validate a prototype technology as a serodiagnosis platform for syphilis. Five peptides were used as antigens in a peptide-based ELISA against serum samples from syphilis-positive or noninfected patients (n = 122). CETp0435 achieved 100% sensitivity and specificity with a high accuracy. The peptides CETp0171 and CETp0574 demonstrated high diagnostic performance, with sensitivity above 83% and specificity >90%. Peptides CETp0684 and CETp0453 exhibited sensitivity above 80% and 90%, respectively; CETp0453 showed reduced specificity (∼66%). The peptides CETp0435 and CETp0171 maintained high diagnostic accuracy across syphilis stages, with a sensitivity above 83% and a specificity exceeding 97%. Peptides CETp0435 and CETp0171 effectively monitored syphilis treatment, as evidenced by the significant post-treatment decline in serum antibody levels, supporting their potential for evaluating the therapeutic efficacy. We obtained two epitopes mimetic peptides as advantageous antigens for serodiagnosis and treatment monitoring.

梅毒螺旋体脂蛋白抗原表位设计对梅毒诊断和治疗预后的影响。
梅毒是一种多阶段性传播感染,如果不治疗,会导致严重的并发症。由于梅毒螺旋体蛋白含量低,体外培养困难,因此难以准确诊断。免疫蛋白质组学的进步已经确定了提高诊断准确性的关键抗原。利用生物信息学工具设计免疫优势抗原蛋白Tp0171、Tp0435、Tp0574、Tp0684和Tp0453的表位,并化学合成模拟肽。诊断准确性横断面研究进行了验证原型技术作为梅毒血清诊断平台。在一种基于多肽的酶联免疫吸附试验中,用五种多肽作为抗原,对梅毒阳性或未感染患者的血清样本进行检测(n = 122)。CETp0435达到100%的灵敏度和特异性,准确度高。肽CETp0171和CETp0574表现出较高的诊断性能,敏感性83%以上,特异性>90%以上。肽CETp0684和CETp0453的敏感性分别在80%和90%以上;CETp0453的特异性降低(约66%)。肽CETp0435和CETp0171在梅毒分期中保持较高的诊断准确性,敏感性超过83%,特异性超过97%。肽CETp0435和CETp0171有效监测梅毒治疗,治疗后血清抗体水平显著下降证明了这一点,支持了它们评估治疗效果的潜力。我们获得了两个表位模拟肽作为有利抗原用于血清诊断和治疗监测。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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