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

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