Development of Point-of-Care Diagnostics for Norovirus

描述(申请人提供)：诺如病毒是一组无包膜的单链RNA病毒，是胃肠炎爆发的主要原因，每年在美国有2100万例病例。目前的预防和控制选择有限，没有疫苗或治疗方法可用。基于抗体的诺沃克病毒诊断试剂盒灵敏度低，依赖于所使用的抗体。快速、准确、定点诊断试剂盒对于检测和隔离受感染人员至关重要。我们提出了一种利用人工合成的多聚糖作为捕获分子的新方法。在这项提议中，一个跨学科的团队将开发快速的护理点诊断方法，以敏感地检测诺沃克病毒。在具体目标1中，我们将使用模块化合成策略来生成组织血型抗原和Lewis抗原的合成类似物，这两种抗原是诺沃克病毒的附着因子。在特定目标2中，我们将开发和评估基于葡聚糖的诊断平台，在特定目标3中，将使用暴发和零星的胃肠道疾病的临床样本对候选诊断平台进行比较。实现这项提案中的具体目标预计将产生快速、稳健、 护理，用户友好的诊断，以准确和敏感地检测所有人类诺沃克病毒株。 与公共卫生相关：一个跨学科的科学家团队将开发基于葡聚糖的诺沃克病毒诊断方法，诺沃克病毒是一种高度传染性的病原体，导致美国约50%的胃肠道疾病爆发。我们将合成一个糖链文库，将这些糖链整合到多个诊断平台中，并使用一个全面的存档和当代诺沃克病毒株的小组来评估它们的性能。这些特定目标的成功完成预计将导致开发针对不同诺沃克病毒株的快速、强大、用户友好的诊断方法。

DESCRIPTION (provided by applicant): Noroviruses, a group of non-enveloped single-stranded RNA viruses, are the leading cause of gastroenteritis outbreaks and account for 21 million cases in the United States annually. Current prevention and control options are limited with no vaccines or therapeutics available. Antibody-based norovirus diagnostic kits suffer from low sensitivity and are dependent on the antibody used. Rapid, accurate, point-of-care diagnostic kits are critical to detect and isolate infected personnel. We propose a novel approach by using synthetic glycans as capture molecules. In this proposal, an interdisciplinary team will develop rapid, point-of-care diagnostics for the sensitive detection of norovirus. In Specific Aim 1, we will use a modular synthetic strategy to generate synthetic analogs of histo-blood group antigens and Lewis antigens, attachment factors for norovirus. In Specific Aim 2, we will develop and evaluate glycan based diagnostic platforms using panels of norovirus strains In Specific Aim 3, candidate diagnostic platforms will be compared side-by-side evaluated using clinical samples from both outbreaks and sporadic cases of gastrointestinal illness. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise and sensitive detection of all human norovirus strains. PUBLIC HEALTH RELEVANCE: An interdisciplinary team of scientists will develop glycan-based diagnostics for norovirus, a highly infectious pathogen that causes ~50% of all gastrointestinal outbreaks in the United States. We will synthesize a library of glycans, incorporate these glycans into multiple diagnostic platforms and evaluate their performance using a comprehensive panel of archived and contemporary norovirus strains. Successful completion of these specific aims is expected to lead to the development of rapid, robust, user-friendly diagnostics for different strains of norovirus.