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NAB-SPEAR: Measuring the Strength of COVID-19 Immune Responses

Novel assay can be performed using a single drop of blood and standard lab equipment

Vaccinations to protect people from the novel SARS-CoV-2 virus are well underway, but many outstanding questions have yet to be answered: how can a patient know if their body has mounted an effective immune response? How long does that immune response last? Is a person “safe” from COVID-19 after their first vaccine dose? Will their vaccination protect them against other mutant strains of the virus?

NAB-SPEAR: Measuring the Strength of COVID-19 Immune Responses
Neutralizing antibodies (NABs) bind directly to the portion of the SARS-CoV-2 Spike protein that the virus uses to attach to and infect cells. Determining whether a patient’s antibodies are NABs and the strength of their binding is crucial for understanding how long an immune response against COVID-19 lasts. Credit: Wyss Institute at Harvard University

Answers to those questions require measurement of neutralizing antibodies (NABs), molecules in the blood that specifically prevent SARS-CoV-2 spike proteins from binding to human cells. Current methods to measure NABs require that a patient go to a specialized lab for a phlebotomist-drawn blood sample, and the subsequent analysis can take days. A faster, simpler, more widely-available NAB assay is required to address the global scope of the COVID-19 pandemic and confirm that vaccines provide effective, lasting protection.

Faster, better, cheaper antibody testing

NAB-SPEAR is a novel, ultrasensitive antibody assay technology that can measure the presence and activity of NABs against the SARS-CoV-2 spike protein. NAB-SPEAR leverages a simple, rapid workflow comprising a homogenous assay with no washing or separation steps, followed by a quantitative, ultrasensitive readout using standard laboratory equipment with which current COVID-19 molecular diagnostic tests (PCR) are performed. NAB-SPEAR employs an innovative “double handshake” method to eliminate the random interactions that typically limit the performance of homogeneous assays, allowing precise measurement of how effectively a patient’s NABs are binding to the correct part of the Spike protein.

The extraordinary sensitivity of NAB-SPEAR enables measurements to be carried out on a single drop of blood, eliminating the need for patients to go to specialized labs. Instead, samples can be taken at home and subsequently dropped off at (or even mailed to) a lab. Moreover, the simple workflow of NAB-SPEAR allows it to be easily automated to process at least 50,000 samples daily.

Beyond its near-term applicability to SARS-CoV-2, NAB-SPEAR has long-term value as a tool for developing and testing vaccines against other pathogens. It can also be used to assess whether patients have an unwanted immune reaction to a protein-based therapeutic.

This technology is currently being de-risked at the Wyss Institute.

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