Song Yunfeng, Singh Pankaj, Nelson Eric, Ramamoorthy Sheela
Department of Veterinary and Microbiological Sciences, North Dakota State University, Dakota State University, Fargo, North Dakota, USA College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Department of Veterinary and Microbiological Sciences, North Dakota State University, Dakota State University, Fargo, North Dakota, USA.
J Clin Microbiol. 2016 Aug;54(8):2039-46. doi: 10.1128/JCM.00460-16. Epub 2016 May 25.
The periodic emergence of new infectious agents and the genetic and antigenic evolution of existing agents necessitate the improvement of technology for the rapid development of diagnostic assays. The porcine epidemic diarrhea virus (PEDV) emerged in the United States in 2013, causing severe economic damage to the pork industry. The primary goal of this study was to develop methods to reduce the lead time for serological assay development. An approach involving the computational prediction of diagnostic targets, followed by a rapid synthesis of antigens, was adopted to achieve this objective. To avoid cross-reactivity with other closely related swine coronaviruses, the N protein sequences of PEDV were analyzed to identify sequences unique to PEDV. The potential antigenicity of the identified sequence was predicted computationally using the Jameson-Wolf method. A sequence with a high antigenic index was rapidly synthesized using an in vitro transcription and translation system to yield the diagnostic antigen. The computationally designed enzyme-linked immunosorbent assay (ELISA) was validated using 169 field sera, whose statuses were determined by a PEDV-specific immunofluorescence assay. Comparison of the computationally designed ELISA to a conventionally developed ELISA, using bacterially expressed N protein, and to the immunofluorescence assay showed a high degree of agreement among the three tests (mean kappa statistic, 0.842). The sensitivity and specificity, compared to the conventionally developed assay, were 90.62 and 95.18, respectively. Therefore, the described approach is useful in reducing the development time for serological assays in the face of an infectious disease outbreak.
新传染病原体的周期性出现以及现有病原体的基因和抗原进化,使得快速开发诊断检测技术的改进成为必要。猪流行性腹泻病毒(PEDV)于2013年在美国出现,给猪肉行业造成了严重的经济损失。本研究的主要目标是开发方法以缩短血清学检测开发的前置时间。采用了一种先通过计算预测诊断靶点,随后快速合成抗原的方法来实现这一目标。为避免与其他密切相关的猪冠状病毒发生交叉反应,对PEDV的N蛋白序列进行了分析,以鉴定PEDV特有的序列。使用詹姆森-沃尔夫方法通过计算预测所鉴定序列的潜在抗原性。利用体外转录和翻译系统快速合成具有高抗原指数的序列,以产生诊断抗原。使用169份现场血清对通过计算设计的酶联免疫吸附测定(ELISA)进行验证,这些血清的状态通过PEDV特异性免疫荧光测定来确定。将通过计算设计的ELISA与使用细菌表达的N蛋白常规开发的ELISA以及免疫荧光测定进行比较,结果显示这三种检测方法之间具有高度一致性(平均kappa统计量为0.842)。与常规开发的检测方法相比,其敏感性和特异性分别为90.62和95.18。因此,所描述的方法对于在传染病爆发时缩短血清学检测的开发时间是有用的。