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一种新型重组多表位嵌合蛋白是钩端螺旋体病血清学诊断的有前景的标志物。

A New Recombinant Multiepitope Chimeric Protein of Is a Promising Marker for the Serodiagnosis of Leptospirosis.

作者信息

Fernandes Luis G V, Avelar Kátia E S, Romero Eliete C, Heinemann Marcos B, Kirchgatter Karin, Nascimento Ana L T O

机构信息

Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, Avenida Vital Brazil, 1500, Sao Paulo 05503-900, SP, Brazil.

Laboratório de Referência Nacional para Leptospirose, Instituto Oswaldo Cruz-Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, RJ, Brazil.

出版信息

Trop Med Infect Dis. 2022 Nov 9;7(11):362. doi: 10.3390/tropicalmed7110362.

Abstract

The zoonotic disease leptospirosis is caused by pathogenic species of the genus and was recently included in the list of Neglected Diseases by the World Health Organization. Leptospirosis burden is estimated to have over a million human cases and cause 60 thousand deaths annually, in addition to its economic impact and veterinary concern. The microscopic agglutination test (MAT), recommended by the World Health Organization, exhibits reduced sensitivity at the beginning of the disease, in addition to being technically difficult. New recombinant antigens are being pursued for rapid and specific serodiagnostic tests, especially in the initial phase of the disease, and chimeric multiepitope proteins are a strategy with a great potential to be implemented in serology. Based on previous subproteomic results, we designed a synthetic construct comprising 10 conserved leptospiral surface antigens, and the recombinant protein was purified and evaluated regarding its diagnostic potential. The protein termed rChi2 was recognized by antibodies in serum from patients both at the onset (MAT-) and in the convalescent (MAT+) phase in 75 and 82% of responders, respectively. In addition, rChi2 immunization in hamsters elicited a strong humoral response, and anti-rChi2 antibodies recognized several immobilized intact species, validating its potential as an early, broad, and cross-reactive diagnostic test.

摘要

人畜共患病钩端螺旋体病由钩端螺旋体属的致病物种引起,最近被世界卫生组织列入被忽视疾病名单。据估计,钩端螺旋体病负担每年导致超过100万例人类病例并造成6万例死亡,此外还具有经济影响并引发兽医关注。世界卫生组织推荐的显微镜凝集试验(MAT)在疾病初期敏感性降低,而且技术难度大。正在寻求新的重组抗原来进行快速和特异性血清诊断测试,特别是在疾病的初始阶段,嵌合多表位蛋白是一种很有潜力在血清学中实施的策略。基于先前的亚蛋白质组学结果,我们设计了一种包含10种保守钩端螺旋体表面抗原的合成构建体,并对重组蛋白进行了纯化,并评估了其诊断潜力。名为rChi2的蛋白在发病期(MAT阴性)和恢复期(MAT阳性)患者血清中的抗体识别率分别为75%和82%。此外,仓鼠接种rChi2可引发强烈的体液反应,抗rChi2抗体识别几种固定化的完整钩端螺旋体物种,证实了其作为早期、广泛和交叉反应性诊断测试的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f66/9694704/7b68881e57cc/tropicalmed-07-00362-g001.jpg

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