NEW YORK – A team of researchers from the Singapore-MIT Alliance in Research and Technology (SMART) has created a 10-minute test that can determine someone's immunity to SARS-CoV-2 and its variants and indicate whether an additional vaccine dose is needed.
SMART, created by the Massachusetts Institute of Technology in partnership with the National Research Foundation of Singapore, is a research hub with multiple interdisciplinary research groups.
Drawing on work they began before the pandemic to detect other infectious diseases, the researchers from SMART's Antimicrobial Resistance Interdisciplinary Research Group, along with collaborators from Nanyang Technological University, Singapore, created a test that can both detect the presence of and quantify the concentration of neutralizing antibodies to SARS-CoV-2 from a fingerstick sample. Details on the test's development and validation were published in a paper in Bioengineering and Translational Medicine earlier this year.
The assay's application to measure the efficacy of vaccine boosters against SARS-CoV-2 variants was laid out in a paper published last month in Microbiology Spectrum. The paper covers two separate studies: one to measure the waning efficacy of SARS-CoV-2 vaccines against the wild-type virus after two doses, and one to evaluate the antibody response against both the wild-type virus and variants of concern after one month and more than three months post-booster.
The test uses cellulose paper coated with chemicals that bind to the antibodies in the blood sample, as well as an instrument that automates the results readout to provide the quantitative value of the antibody concentration.
The surface of the cellulose paper contains a reagent that mimics the receptor-binding domain of the virus's spike protein, while a separate reagent in the solution that the blood sample is mixed with mimics human ACE2 receptor proteins, said Hadley Sikes, an associate professor at MIT and a co-corresponding author on both papers. If the neutralizing antibodies are present in the sample, they will block the interaction between the reagent on the paper's surface and the reagent in the solution and generate a signal indicating that the reaction was blocked.
While the first iteration of the test had a visual readout, the researchers didn't want the results to be susceptible to human error, so they designed an instrument that would automate the readout, Sikes, who is also the principal investigator of the SMART AMR group, said.
The test works for all known variants of SARS-CoV-2 — since each variant has mutations in the spike protein, the team has integrated reagents that mimic the response of neutralizing antibodies to each variant into the test, and as new variants crop up, additional reagents can be added to ensure it works with them, Sikes said. In addition, the test showed sensitivity above 80 percent and accuracy of 93 percent in last year's paper compared to a laboratory-based antibody test.
The quantitative measurement of the assay is a benefit since the test isn't just measuring the presence of antibodies but the percent of the interaction that is being blocked by those antibodies, which indicates the level of immunity to infection. "The measurement has functional significance," she noted.
Due to its speed and the fact that the sample requires no processing before the test is run, Sikes said she sees the assay being used primarily in point-of-care settings. A user doesn't need laboratory training to perform the test, either — the cartridge with the blood sample that has been treated with reagents is simply inserted into the instrument to get a result.
The Microbiology Spectrum paper applied the test to determine patient responses to SARS-CoV-2 and its variants after receiving booster vaccinations. The test "can guide decisions on the potential need for booster vaccinations at an individual level," the researchers wrote.
SARS-CoV-2 antibody tests were of great interest to the diagnostics community early in the pandemic, with companies like Roche, Siemens Healthineers, and Abbott launching serology tests, but demand has waned due to a lack of obvious medical necessity and confusion about how exactly antibody levels correlate to protection from infection. According to Benjamin Larman, an associate professor of immunopathology at Johns Hopkins School of Medicine, there's some "limited demand [to] check for reactivity against the nucleocapsid protein, which can distinguish infection from vaccination," but "since current antibody tests do not provide reliable information about protection," that demand has declined.
He noted via email that the most commonly available antibody tests are semi-quantitative binding assays that don't correlate as well with protection. However, the SMART test is a more complex functional test that "could provide more useful information, assuming the performance is very good." However, Larman said that this type of test is a "surrogate for neutralizing activity," meaning that "even the best of such tests cannot perfectly capture one's true level of protection, which also depends on many other components of the immune system."
The SMART researchers aren't the only ones developing point-of-care neutralizing antibody tests — researchers out of Australia published a paper in eBioMedicine in December about the development of a lateral flow assay to measure levels of neutralizing antibodies from whole blood.
Larman said he wasn't sure about how much the SMART test would be adopted in a clinical setting, but that the consumer market could be interested, particularly if the performance is high and cost is low, as people want to "know more precisely how protected they are, which might guide their behavior."
He added that it will be important to clearly understand the limitations of the test in the real world. "For example, when someone's test result is positive, but their antibodies don't actually neutralize as well as predicted, how often would that person then put themselves at risk and acquire a harmful infection?" he asked.
The researchers, however, believe the assay has the potential to make a difference, particularly when it comes to vaccination efforts. The test has been licensed to a SMART spinout company, Thrixen, which has plans to commercialize it globally, Sikes said. Patthara Kongsuphol, Thrixen's director, said via email that the company plans to start commercializing the test — as the CoVIm System — in Singapore, Southeast Asia, and the Asia-Pacific region before expanding to Europe and possibly the US.
The firm is currently collecting clinical data and preparing to submit the test to regulatory bodies in Asia, Kongsuphol added. The test will be distributed as a combination of the test cartridge and instrument, and should be in a similar price range to standard rapid tests that are currently available. Thrixen also plans to commercialize tests for other diseases on the platform in the future, Kongsuphol said.
Originally, the researchers had applied their technology to malaria, Zika virus, and tuberculosis, Sikes noted. Those tests were being commercialized before the pandemic, and plans to commercialize them are ongoing. The platform they've developed can be used for other diseases as well, she added. "As long as the biomarker is known and we can make the reagents," a test can be developed.