Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis
Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis
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DOI：
10.1186/s13071-020-04138-7
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发表时间：
2020-05-30
影响因子：
3.2
通讯作者：
Ali, Nahid
中科院分区：
文献类型：
--
作者：
Ejazi, Sarfaraz Ahmad;Ghosh, Smriti;Ali, Nahid
背景内脏利什曼病(VL)是一种寄生虫病，如果延误治疗会造成严重的医学后果。尽管印度次大陆的VL病例数量有所下降，但这种疾病在较新地区的开始仍然是一个主要关切。虽然以免疫层析试验为主的血清学诊断已被发现是有效的，但在治疗的不同阶段进行治愈试验仍然是必要的。尽管一些候选疫苗已经在小鼠模型中获得了良好的预防反应，但很少有人提议将其用于人类。方法用电洗脱法对利什曼原虫前鞭毛体膜抗原(LAG)的9个抗原组分(31、34、36、45、51、63、72、91和97 kDa)进行电洗脱，并对治愈后1个月和治疗后6个月的活动性VL进行诊断和鉴别。为了进一步研究电洗脱蛋白的免疫原性，用31、34、51、63、72和91 kDa的蛋白刺激治愈的VL患者的PBMC。结果34 kDa和51 kDa蛋白对健康对照和其他疾病的敏感性和特异性均为100%。治疗6个月后，72和91 kDa抗原的抗体显著下降，几乎降至正常水平。提示34 kDa和51 kDa蛋白可用于诊断，而72 kDa和91 kDa蛋白可用于监测治疗结果。在另一种检测中，51 kDa和63 kDa蛋白表现出最大的上调干扰素-γ和IL-12的能力，而诱导IL-10和转化生长因子-β的能力最低。结果表明，51 kDa和63 kDa蛋白可能是人类免疫VL的有力候选者。相比之下，34和91 kDa的蛋白质表现出相反的特征，可能不是一个好的疫苗候选。结论本研究获得的初步数据表明，部分抗原可用于利什曼原虫的诊断和治疗试验。此外，一些抗原通过T细胞介导的免疫反应表现出良好的免疫预防细胞因子的产生，这表明VL未来的疫苗候选。然而，需要进一步的研究来探索这些抗原在诊断中的作用，并获得长期的免疫反应。
Background Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. Results We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-gamma and IL-12 with minimum induction of IL-10 and TGF-beta. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.