Donnelly Investigators are Developing Rapid, Sensitive Antibody Test for COVID-19

A prick of blood that lights up in the presence of SARS-CoV-2 antibodies is being developed at U of T to help boost Canada’s immune-surveillance.

Donnelly Centre investigators are developing a rapid blood test that can detect in under an hour if a person has been infected with SARS-CoV-2 and developed antibodies to it. Such serological tests are seen by many world countries as key for easing physical distancing measures and restarting the economy.

“Until we have a valid drug treatment strategy or vaccine against COVID-19, we will have to perform mass blood testing in our corresponding countries,” says Igor Stagljar, a professor of biochemistry and molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research, who leads the effort with support from Toronto COVID-19 Action Fund.

“These serological tests will be the only way we can reliably determine the extent of viral spread and identify those individuals who are able to safely return to work,” says Stagljar.

Serological tests look for antibodies in blood that are produced by the body to fight infection. Antibodies are protein molecules that bind and neutralize foreign proteins, known as antigens, that come from viruses and other pathogens.

According to the plan outlined by the federal immunity taskforce, at least one million serological tests will be carried out over the next two years to help gauge how many Canadians have been exposed to the novel coronavirus.

Earlier this week, Health Canada announced it approved the first serological test for COVID-19. However, concerns have been raised over some methods regarding their ability to detect potentially low antibody levels in people who were recently infected or suffered mild or no symptoms.

“Ideally we want to have a test that is very fast, low cost and accurate,” says Stagljar, whose team is working to achieve just that.

The test involves dousing a blood sample with purified SARS-CoV-2 proteins so that antibodies can bind to them. The viral proteins are engineered to carry pieces of a fluorescent protein that can only be reconstituted if antibodies are present in a chemical reaction that produces a flash of light—a positive result— which is detected by a plate reader instrument.

The test also employs a new technology called SIMPL, for split intein mediated protein ligation developed by Stagljar’s team and described this week in a study published in the journal Nature Communications. SIMPL helps strengthen the contact between antibodies and viral proteins to increase test sensitivity.

“We originally devised SIMPL to study interactions between proteins in living cells, however, we quickly realized that the technology could be adapted to dramatically improve the sensitivity of a COVID-19 serological assay” says Zhong Yao, a senior research associate in Stagljar’s lab responsible for both the COVID-19 and SIMPL projects.

The prototype lab test can detect different types of antibodies such as immunoglobulinM and immunoglobulinG that can help distinguish how long ago an infection occurred. IgM antibodies are produced first and are relatively short-lived, while IgG antibodies come later and linger in the bloodstream to confer longer-lasting immunity. While is still unclear how long the immunity to COVID-19 lasts, serological tests will help answer this.

“Our goal is to detect IgM and IgG antibodies in only 10 microliters of blood,” says Stagljar. Having validated their test with purified antibodies, the team are now calibrating it for the detection of variable antibody levels in patient blood samples. “We should know in four months if it’s working or not.”

Stagljar is collaborating with Drs. Samira Mubareka and Mario Ostrowski, of the Sunnybrook Health Sciences Centre and St. Michael’s Hospital, respectively, and James Rini, a professor of molecular genetics at U of T’s Faculty of Medicine.

The new SIMPL method locks interacting proteins into a permanent contact to help capture transient protein interactions in cells that could not be detected with other methods. It can also be applied across different types of human cells and to study interactions that occur in different cellular compartments.

Aside from the antibody test, Stagljar is applying SIMPL for cancer drug discovery. One project is looking for small molecules that can inhibit protein interactions involving disease variants of the KRAS protein, which is mutated in a third of all cancers. The project has received funding from the Cancer Research Society, FACIT Oncology Fund, Genome Canada and Toronto Innovation Acceleration Partners, a public-private partnership supporting academic research commercialization and previously known as Mars Innovation.

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