With this reaction, a glucose meter can detect SARS-CoV-2 antibodies in patient samples. (Ab=antibody; Inv=invertase). Credit: Adapted from Journal of the American Chemical Society 2022, DOI: 10.1021/jacs.2c02537
If you received a vaccination for SARS-CoV-2 back in late 2020 or early 2021, odds are you have no antibodies left to fight off the virus, especially given the variants that have emerged since. However, if you contracted SARS-CoV-2 say 4 months ago (even with the vaccine and booster), are you protected against reinfection?
Despite the immense amount of R&D put into COVID-19 at this point, the answer to that question is still unclear. Researchers have not been able to nail down the variables that contribute to immune protection longevity—or lack thereof. The most current data suggests the factors may be highly individualized, complicating the matter further.
On a population-wide level, this data is important as it can deepen epidemiological understanding of COVID-19 and help construct public health and vaccination recommendations in both the near- and long-term. But, there are no at-home tests for SARS-CoV-2 antibodies and the gold standard—enzyme-linked immunosorbent assays (ELISA)—require expensive equipment and specialized technicians.
Researchers at Johns Hopkins University developed an innovative solution using a common device with a novel twist—a simple glucose meter-based test incorporating a novel fusion protein they say consumers could someday use to monitor their own SARS-CoV-2 antibody levels.
For years, scientists have been adapting glucose meters to sense other target molecules, coupling detection with glucose production. For example, if a detection antibody in the test binds to an antibody in a patient’s blood, then a reaction occurs that produces glucose—something the device detects very well. On paper, invertase is the perfect enzyme for this type of analysis because it converts sucrose into glucose, but scientists have had trouble with it. When they try to couple invertase to detection molecules using chemical approaches, the enzyme turns inefficient and inconsistent.
Thus, lead author Elissa Leonard and her team designed and produced a novel fusion protein containing both invertase and a mouse antibody that binds to human immunoglobulin (IgG) antibodies. In their paper, published in Journal of the American Chemical Society, the team showed that the fusion protein bound to human IgGs and successfully produced glucose from sucrose.
To demonstrate the diagnostic potential of the protein, the researchers devised test strips with the SARS-CoV-2 spike protein on them. When dipped in COVID-19 samples, the patients’ SARS-CoV-2 antibodies bound to the spike protein. Adding the invertase/IgG fusion protein follow by sucrose led to the production of glucose, which was easily detected by the meter. The team validated the test by performing the analysis with glucose meters on a variety of patient samples, and found that the new assay performed as well as four different ELISAs.
“This study represents one of the first instances in which a full-length antibody is genetically fused to an enzyme for the purposes of detection,” the researchers write in their paper, pointing out that only one other platform has been developed with these capabilities—but that system links the enzyme to immunoglobulin M (IgMs), which naturally have low affinity compared with IgGs and are more difficult to produce.
The researchers say their simple glucose meter-based method can be adapted to test for other antigens, including SARS-CoV-2 variants and other infectious diseases, as well as those associated with cancer diagnostics and autoimmune diseases.
In the meantime, the low technical requirements and low production cost of the new system means a much larger number of people can be tested for antibodies that ever before, including those who do not have access to medical facilities with advanced testing capabilities.
“It will also empower serial testing, which combined with the number and diversity of people being tested will provide needed high-quality data to impart a clear and detailed understanding of the longevity of immune protection that is provided from vaccination and natural infection, as well as protection against emerging variants of concern,” conclude the study authors.
The Massachusetts-based team says further device development efforts will focus on simplifying the detection scheme so that the fusion protein and other reagents can be integrated into a portable, user-friendly, point-of-need detection platform.