Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Diagnostic Global Program, PATH, Seattle, Washington.
J Infect Dis. 2020 May 11;221(11):1805-1815. doi: 10.1093/infdis/jiz307.
Serological assessments for human onchocerciasis are based on IgG4 reactivity against the OV-16 antigen, with sensitivities of 60-80%. We have previously identified 7 novel proteins that could improve serodiagnosis.
IgG4 responses to these 7 proteins were assessed by luciferase immunoprecipitation (LIPS) and enzyme-linked immunosorbent (ELISA) immunoassays.
OVOC10469 and OVOC3261 were identified as the most promising candidates by IgG4-based immunoassays with sensitivities of 53% for rOVOC10469 and 78% for rOVOC3261 while specificity for each was >99%. These 2 antigens in combination with OV-16 increased the sensitivity for patent infections to 94%. The kinetics of appearance of these IgG4 responses based on experimentally infected non-human primates indicated that they were microfilarial- driven. Further, the IgG4 responses to both OVOC10469 and OVOC3261 (as well as to OV-16) drop significantly (p<0.05) following successful treatment for onchocerciasis. A prototype lateral flow rapid diagnostic test to detect IgG4 to both Ov-16 and OVOC3261 was developed and tested demonstrating an overall 94% sensitivity.
The combined use of rOVOC3261 with OV-16 improved serologic assessment of O. volvulus infection, a current unmet need toward the goal of elimination of transmission of O. volvulus.
针对人体盘尾丝虫病的血清学评估基于针对 OV-16 抗原的 IgG4 反应性,其敏感性为 60-80%。我们之前已经确定了 7 种可能改善血清诊断的新蛋白。
通过 luciferase immunoprecipitation (LIPS) 和 enzyme-linked immunosorbent (ELISA) 免疫测定评估这 7 种蛋白的 IgG4 反应。
在 IgG4 为基础的免疫测定中,OVOC10469 和 OVOC3261 被鉴定为最有前途的候选物,rOVOC10469 的敏感性为 53%,rOVOC3261 的敏感性为 78%,而每种抗原的特异性均>99%。这两种抗原与 OV-16 联合使用可将对有症状感染的敏感性提高到 94%。基于实验性感染的非人类灵长类动物的这些 IgG4 反应出现的动力学表明它们是微丝蚴驱动的。此外,针对 OVOC10469 和 OVOC3261(以及 OV-16)的 IgG4 反应在成功治疗盘尾丝虫病后显著下降(p<0.05)。开发并测试了一种用于检测 IgG4 对 Ov-16 和 OVOC3261 的原型侧向流动快速诊断测试,总体敏感性为 94%。
rOVOC3261 与 OV-16 的联合使用改善了对 O. volvulus 感染的血清学评估,这是消除 O. volvulus 传播目标的当前未满足的需求。