- Current assays that can accurately measure antibody levels against SARS-CoV-2—the virus that causes COVID-19—are costly, time-consuming, and require sophisticated detection systems.
- However, scientists have now developed a rapid and cost-effective antibody assay that can quantify antibody levels with the help of glucose meters commonly used for measuring blood sugar levels.
- The sensitivity of this new glucose meter-based antibody assay was similar to current ‘gold standard’ assays, and the test could also be adapted for other medical conditions.
Researchers at Johns Hopkins University have developed a novel rapid assay that can detect antibodies against SARS-CoV-2 using widely-available glucose meters. This novel glucose meter-based antibody assay is easier to perform and more cost-effective than the current gold-standard assays.
One of the study’s co-authors Dr. Jamie Spangler, professor at Johns Hopkins University, said, “This work presents an innovative approach towards democratizing the availability of immune protection data by enlisting commercial glucometers to quantitatively measure levels of disease-targeted antibodies.”
Dr. Eliah Aronoff-Spencer, a professor of medicine at the University of California, San Diego, said, “While there are notable barriers to the development of fieldable diagnostics using off-the-shelf glucometers, studies such as these highlight a possible future where home diagnosis is as cheap and accurate as glucose sensing. At this point, we will have a transformation in global surveillance and personal disease detection.”
The study appears in the Journal of the American Chemical Society.
Quantifying antibody levels
The tests for diagnosing COVID-19 detect the presence of viral genetic material or proteins. In contrast, assays measuring antibodies against SARS-CoV-2 can help assess past exposure to the virus.
These antibodies include IgG antibodies, which are the predominant type of antibodies present in the blood. IgG antibodies play a vital role in producing an immune response against bacteria and viruses, including SARS-CoV-2.
Notably, these IgG antibodies persist for months after a SARS-CoV-2 infection or after receiving a COVID-19 vaccine.
The IgG antibody levels are predictive of the degree of protection against a symptomatic SARS-CoV-2 infection. Thus, evaluating antibody levels in the population can help determine how long immunity against COVID-19 persists after vaccination or a previous infection.
The emergence of new SARS-CoV-2 variants has also raised fears about waning immunity, making it crucial to assess levels of immune protection in the population. Determining antibody levels against SARS-CoV-2 could thus help to guide policy decisions about the need for booster shots.
Enzyme-linked immunosorbent assays (ELISAs) are the gold standard for measuring antibody levels. However, accurately quantifying antibody levels using ELISAs requires blood samples to be sent to specialized laboratories due to the need for expensive detection devices. As a result, conducting these assays is time-consuming, costly, and requires skilled technicians.
Although rapid ELISA tests have been developed for use in the clinic, these tests only provide qualitative information and remain costly. Thus, there is a need for cost-effective and broadly accessible alternatives to ELISAs that can be used by clinicians or the general public.
How glucose meters help
To overcome these limitations associated with ELISAs, scientists have developed tests that are compatible with glucose meters. Using commercially available glucose meters for antibody detection can reduce the cost of detection and the need for skilled technicians.
These tests involve antibodies or other detection molecules coupled with the enzyme invertase which breaks down sucrose or sugar into glucose. The antibodies coupled with invertase bind to the protein of interest in a sample and produce glucose upon the introduction of a sucrose solution. The amount of glucose produced is proportional to the amount of protein of interest and can be detected by a glucose meter.
Coupling antibodies with invertase, however, has proved difficult. In some studies, researchers have indirectly coupled invertase with antibodies with the help of intermediate compounds such as nanoparticles. However, such an approach can cause variation in the amount of coupling and produces inconsistent results.
Researchers at Johns Hopkins University have now developed a novel assay involving antibodies that are directly coupled with two invertase molecules. The researchers used genetically modified laboratory cultured cells to express these antibodies fused with invertase molecules.
In contrast to indirect coupling, the genetic fusion of the antibody and invertase enzyme ensures that a consistent number of invertase molecules are attached to the antibody. These antibodies coupled with invertase can bind to all human IgG antibodies.
The novel assay uses a plastic strip coated with the SARS-CoV-2 spike protein. Upon incubation of the strip with blood samples from those with a history of COVID-19, the SARS-CoV-2-specific antibodies selectively bind to the spike proteins coating the surface of the strip.
After rinsing the strip to remove the non-specific antibodies, the strip is first transferred to a solution containing the antibody-invertase fusion protein, and then to a sucrose solution.
The SARS-CoV-2-specific IgG antibodies bound to the spike protein on the strip can then be detected by the antibody-invertase fusion protein. The invertase enzyme subsequently breaks down sucrose into glucose, which can be detected using a glucose meter. The assay produces glucose in proportion to the SARS-CoV-2 specific IgG antibodies in the blood sample.
In the present study, the researchers found that the glucose meter-based antibody-invertase protein assay could accurately detect IgG antibodies against SARS-CoV-2 and its performance was comparable with commercially available ELISAs.
Potential for other diseases
The antibody-invertase fusion protein recognizes all IgG antibodies produced by the human body, making this assay versatile.
“The immediate goal for this technology is to scale up manufacturing to allow for broad deployment. We hope to use emergent data from this platform to correlate disease protection with antibody levels across a wide range of subjects,” Dr. Spangler said.
The assay could be used against other conditions by coating the strip with a protein other than the wild-type SARS-CoV-2 spike protein. For instance, strips coated with the spike protein from a SARS-CoV-2 variant could be used to measure antibody levels against that variant.
“We envision that the assay we have developed could be adapted to detect antibodies against future variants of the SARS-CoV-2 virus as well as against other infectious diseases. The assay could also be used to detect antibodies in the context of other conditions such as cancer, autoimmune disorders, allergy, or transplantation.”
— Dr. Jamie Spangler
“This technology can offer important scientific insights and also inform decisions related to medical interventions and public health policies. Furthermore, the versatile nature of this platform allows it to be readily adapted to target a variety of disease applications beyond infection,” added Dr. Spangler.
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