Rapid SARS-CoV-2 Spike Protein Neutralizing Antibody Tests for Evaluating COVID Vaccine-Generated Immunity

用于评估 COVID 疫苗产生的免疫力的快速 SARS-CoV-2 刺突蛋白中和抗体测试

• 批准号: 10384304
• 负责人: Suiqiong Li
• 金额: $ 24.21万
• 依托单位: DL ADV-TECH, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384304
• 关键词: Rapid; SARS; CoV; Spike; Protein

Summary/Abstract: The availability of COVID-19 vaccines is a significant step in ending this pandemic and returning life to normal. Successfully vaccination should induce sufficient titers of specific neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to prevent infection of COVID-19. SARS-CoV-2 spike protein nAbs test will be essential to verify whether the recipients have sufficient protection and determine the duration of immunity. Conventional SARS-CoV-2 spike protein nAbs test, such as plaque reduction neutralization test and ELISA, are laboratory based, which are not suitable for large scale measurement. While lateral flow assays can provide cheap and quick tests, current lateral flow test strips can’t provide accurate quantitative measurement. In this SBIR project, DL ADV-Tech proposes to develop a highly sensitive, reliable and rapid SARS-CoV-2 S-protein nAbs testing device for quantification of nAbs concentrations. The major significance of this proposed approach is the ability to accurately, quickly and massively quantify SARS-CoV-2 S-protein nAbs by leveraging our advanced mesoporous nanoflowers (MNFs) signal amplification technique (patent pending) and smartphone-based readout technique. Recently we discovered a new class of catalytic nanomaterials, bimetal Pt-Pd MNFs, with impressive peroxidase-like catalytic activity and excellent stability under harsh conditions. Our patent pending “bimetal MNFs-based lateral flow immunoassays” demonstrated Pt-Pd MNFs can improve the sensitivity by 1000 times over commercial colloidal gold labels. The tremendous activity of MNFs is of particular importance to make this proposed test platform substantially more compelling for improvement of accuracy in rapid analysis. Meanwhile, the chromatic results from the lateral flow strips will be acquired and analyzed using a smartphone readout, which allows rapid and accurate quantification of SARS-CoV-2 S-protein nAb concentrations. Integrated with smartphone, this testing device will provide quantitative measurements and easy operation, and allow real-time data collection and sharing. The proposed testing device allows highly reliable, simple, robust and quantitative measurement of SARS-CoV-2 S-protein nAbs in blood, providing a powerful tool to accurately and closely monitor SARS-CoV-2 S-protein nAbs levels at a large population scale and offering more confidence to individuals and clinicians to fight this pandemic. In Phase I, the key focus is to prove the concept of rapid quantification of SARS-CoV-2 S-protein nAbs on the proposed testing device, and demonstrate the feasibility of the testing device in blood samples in terms of sensitivity, accuracy and detection range. The Pt-Pd MNFs enhanced smartphone platform is expected to have high accuracy (< 5% RSD) for SARS-CoV-2 S-protein nAbs quantification (1ng/ml – 100ug/ml). In phase II, the tests will be evaluated using clinic samples and further optimized for real-world applications. The proposed testing device, once validated, will greatly benefit public health in the U.S. as well as worldwide. There is a large market and significant commercial opportunity for such an effective testing device. 1

总结/摘要： COVID-19疫苗的供应是结束这场大流行病和恢复正常生活的重要一步。 成功的疫苗接种应诱导足够滴度的特异性中和抗体（nAbs）， 急性呼吸道综合征冠状病毒2（SARS-CoV-2），以预防COVID-19感染。SARS-CoV-2峰值 蛋白质nAbs测试将是必不可少的，以验证接受者是否有足够的保护，并确定 豁免期。常规SARS-CoV-2刺突蛋白nAbs检测，如空斑减少中和 测试和ELISA是基于实验室的，其不适合于大规模测量。虽然横向流动 测定可以提供廉价和快速的测试，目前的侧向流测试条不能提供准确的定量 测量.在这个SBIR项目中，DL ADV-Tech建议开发一种高度灵敏、可靠和 用于定量nAbs浓度的SARS-CoV-2 S蛋白nAbs快速检测装置。主要 该方法的重要性在于能够准确、快速和大量地量化SARS-CoV-2 利用我们先进的介孔纳米花（MNF）信号放大技术， （专利申请中）和基于智能手机的读出技术。最近我们发现了一类新的催化剂 纳米材料，Pt-Pd MNF，具有令人印象深刻的过氧化物酶样催化活性和优异的稳定性 在恶劣的条件下。我们正在申请专利的“基于MNFs的侧向流免疫测定”证明了 Pt-Pd MNF的灵敏度比商业胶体金标记物提高了1000倍。的巨大 多国部队的活动对于使这个拟议的试验平台更加引人注目具有特别重要的意义 以提高快速分析的准确性。与此同时，从横向流条的色彩结果将 使用智能手机读数进行采集和分析，这使得快速准确地定量 SARS-CoV-2 S蛋白nAb浓度。与智能手机集成，该测试设备将提供 定量测量和易于操作，并允许实时数据收集和共享。拟议 检测装置可实现SARS-CoV-2 S蛋白的高度可靠、简单、稳健和定量测量 血液中的nAbs，提供了一个强大的工具，以准确和密切监测SARS-CoV-2 S蛋白nAbs水平， 人口规模大，并为个人和临床医生提供更多的信心来对抗这种流行病。 在第一阶段，关键的焦点是证明SARS-CoV-2 S蛋白nAbs快速定量的概念。 提出的测试装置，并证明了血液样本的测试装置的可行性方面， 灵敏度、准确度和检测范围。Pt-Pd MNF增强型智能手机平台预计将 对SARS-CoV-2 S蛋白nAbs定量（1 ng/ml -100 ug/ml）具有较高的准确度（RSD < 5%）。在第二阶段， 测试将使用临床样本进行评估，并进一步优化现实世界的应用。拟议 这种测试设备一旦得到验证，将极大地有利于美国和世界各地的公共卫生。有一个 这对于这种有效的测试设备来说是巨大的市场和重要的商业机会。 1