The global response to COVID-19 is leading to rapid advances in diagnostic, surveillance, and vaccine and therapeutic development. A critical measurement underpinning much of these efforts is a serological assay that helps to assess the complex patient responses to SARS-CoV-2. Specifically, reliable and rapid serological testing is needed to monitor the spread of the virus, patient immunity against the virus, and to determine the efficacy of vaccines and therapeutics. Yet, serology test results are highly variable for existing serologic tests, in part due to the lack of well characterized globally traceable reference materials needed for validation and assay control. Leveraging our Flow Cytometry Quantitation Consortium and state-of-the-art facilities, we have developed a rapid, multiplexed, and sensitive flow cytometry-based serological assay as well as a BSL-3 sparing neutralization assays (surrogate bead-based neutralization assay and pseudo-virus neutralization assays). This work is supporting the development of the first WHO serology reference materials as well as the work of the NIH/NCI Serology Science Network. These assays also enable the development of a robust measurement infrastructure for serological assays and associated critical reagents.
Multiplexed bead-based SARS-CoV-2 serological assay
We have recently designed and validated a multiplexed bead-based SARS-CoV-2 serological assay that measures different antibodies produced by a patient (IgG, IgM, IgA). In collaboration with the NIST Applied and Computational Mathematics Division, we have developed a new strategy to more confidently classify positive and negative samples. The validated assay was used to characterize a candidate WHO standard through an inter-laboratory study. This assay will also support NCI’s efforts to develop national standards and for the characterization of critical reagents to enable quantitative serology.
BSL-3 sparing neutralization assays
We are working to develop neutralization assays via flow cytometry as well as advanced live cell imaging to assist SARS-CoV-2 vaccine and therapeutic development. These assays will enable the functional assessment of the ability of serum antibodies to prevent cell binding, entry, or other effects of the virus on the cell in vitro. Preliminary data showed excellent correlation between our serology and bead-based neutralization assay results.