人体恰加斯病疫苗候选物的抗原性和诊断潜力。
Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.
机构信息
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
出版信息
PLoS Negl Trop Dis. 2013;7(1):e2018. doi: 10.1371/journal.pntd.0002018. Epub 2013 Jan 17.
BACKGROUND
Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.
METHODS AND RESULTS
Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st)-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd)-phase for antibody response to the recombinant antigens (individually or mixed) by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175). The IgG antibodies to TcG1, TcG2, and TcG4 (individually) and TcG(mix) were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%), TcG2- (96%), TcG4- (94.6%) and TcG(mix)- (98%) based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8%) in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.
CONCLUSIONS
Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.
背景
恰加斯病由克氏锥虫引起，在拉丁美洲流行，是美国和欧洲新出现的传染病。我们已经证明，TcG1、TcG2 和 TcG4 抗原在小鼠和犬中引发针对克氏锥虫的保护性免疫。在此，我们研究了重组蛋白在人类中的抗原性，以确定它们在开发下一代诊断方法筛查克氏锥虫感染和恰加斯病方面的潜在用途。
方法和结果
在第一阶段，用传统血清学检测分析来自阿根廷-玻利维亚和墨西哥-危地马拉流行地区居民的血清样本中针对克氏锥虫的抗体反应；在第二阶段，用 ELISA 分析针对重组抗原（单独或混合）的抗体反应。我们注意到来自阿根廷和墨西哥居民的血清样本中对候选抗原具有相似的抗体反应（n=175）。针对 TcG1、TcG2 和 TcG4（单独）和 TcG（混合）的 IgG 抗体在分别通过传统血清学检测确定为阳性的受试者中分别存在于 62-71%、65-78%和 72-82%和 89-93%的受试者中。基于重组 TcG1-（93.6%）、TcG2-（96%）、TcG4-（94.6%）和 TcG（混合）-（98%）的 ELISA 与基于克氏锥虫锥虫体的 ELISA（77.8%）相比，在诊断克氏锥虫感染和避免与利什曼原虫属交叉反应方面显示出显著更高的特异性。在阳性血清样本中，抗体反应水平与恰加斯病的临床严重程度之间未观察到显著相关性。
结论
来自两个不同研究地点的恰加斯病患者的抗体反应识别了三种候选抗原，并在不同循环寄生虫株中表达。一种检测针对三种抗原的抗体反应的多重 ELISA 法在诊断人类克氏锥虫感染方面具有高度的敏感性和特异性，表明基于 TcG1、TcG2 和 TcG4 重组蛋白的诊断试剂盒将在各种情况下有用。
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