Editor’s note: “Our COVID-19 Fighters” is an occasional series highlighting the ways the CU Anschutz Medical Campus community is helping patients and the wider community in the fight against the pandemic. We welcome your story ideas; please share them here.
Putting their heads and labs together, several groups of researchers from across the University of Colorado Anschutz Medical Campus are working to build a “homegrown” antibody test. Once they do, they say, they are equipped for dispersal to all corners of the state and can help lead the way in corralling the novel coronavirus in Colorado.
Given a shortage of components in the commercial market for developing tests, and a question of accuracy surrounding many of the manufactured kits, the recently formed serology working group sees the approach as a better way to get them back into their labs, solving the many mysteries of the worldwide pandemic.
The collaborative effort involves more than 20 experts from various entities, including UCHealth University of Colorado Hospital and Children’s Hospital Colorado. While they hope to have a test within weeks, members emphasize that the path ahead is long, and an antibody test is only one tool in the battle against COVID-19.
Xiaofan Jia, a researcher in Dr. Liping Yu's lab, fills a vial.
A better approach to a critical mission
“Instead of relying on the commercial supply line for antibody-based testing for past exposure to SARS-CoV-2, we are planning to ‘home grow’ the testing by assembling the components and using resources here on campus,” said Dara Aisner, MD, PhD, associate professor in the Department of Pathology of the virus that causes COVID-19. The same approach has been taken at other leading medical centers, including Mount Sinai and Stanford, she said.
Accurate, widespread antibody testing remains critical for better understanding the novel coronavirus and for guiding epidemiologists and state leaders in making crucial related decisions. An important part of the serology group’s effort includes growing a central biobank on campus for collecting recovered COVID-19 patients’ blood and other biological samples and creating an extensive screening plan.
Campus healthcare and other workers will be tested first, with screening eventually spanning out into the community and across the state through other partnerships, possibly with the 9Health Fair helping to reach rural areas, said Kevin Deane, MD. Deane, along with his Division of Rheumatology colleague Mike Holers, MD, is helping facilitate the working group’s efforts.
Finding the COVID-19 secret wanderers
“We have no idea right now how many Coloradans are walking around with antibodies,” said Ashley Frazer-Abel, PhD, an assistant research professor in the School of Medicine and director of the CAP-accredited Exsera BioLabs on campus. Without that information, critical questions for moving forward are left unanswered, she said.
Because supply of commercial tests for confirming infection failed to meet demand, mostly only hospitalized and high-risk patients have been tested for the virus. With a predicated majority of people contracting the virus having mild or no symptoms, combined with a history of false readings with the initial tests, experts believe many cases are undocumented.
“We have no idea right now how many Coloradans are walking around with antibodies.” – Ashley Frazer-Abel
That suspected void makes accurate calculation of infection and mortality rates impossible, Frazer-Abel said. Moreover, doctors still don’t know for sure if infection provides immunity or for how long, a critical question in social-distancing decision-making and in vaccine and therapeutic research. “This gives us the denominator for answering those questions,” she said.
Building it better, stronger, faster
“All antibody tests are designed a little bit differently and measure slightly different things,” said Brian Harry, MD, PhD, assistant professor in the Department of Pathology, explaining the fundamental basis of developing antibody tests.
“We are looking for antibodies that bind to a viral protein. Many variables, including which protein from the virus researchers select, can ultimately lead to different information, for example related to immunity and protection,” Harry said.
“In the case of COVID-19, the virus has several proteins that are antigenic, meaning that people’s bodies produce antibodies to them,” Aisner said. “Once you’ve figured out what antigen to use to make your test, you make it synthetically.” To perform the rest of the test, researchers use blood from patients who have recovered from COVID-19 to determine whether the antibodies in their blood detect the synthetically made antigen.
Thomas “Tem” Morrison, PhD, associate professor in the Department of Immunology & Microbiology, and his lab provided the working group with the protein and monoclonal antibodies.The Cancer Center Cell Technologies Shared Resource (CTSR) is also critical to the effort, growing and purifying the protein for the Frazer-Abel team.
“The available data suggest that this approach to testing, which uses a different antigen and combines multiple antigens unlike the commercial tests, will have better specificity,” said Aisner, who is working with Harry and Frazer-Abel in Frazer-Abel’s lab. It also allows researchers to customize their own tests for future studies in ways not possible with commercial tests, she said.
As part of the effort, the working group has also been validating commercial antibody tests for the state, and researchers will compare their “home-grown” test with other tests currently in use, said Liping Yu, MD, associate research professor with the Barbara Davis Center for Diabetes (BDC). “If our assay is more specific and more sensitive, then hopefully they will accept our technology to serve the whole state and campus employees.”
Dr. Liping Yu, recognized for his research and testing of autoimmune diseases, poses with fellow researchers Xiaofan Jia (far right) and Dongmei Miao (back) in his campus lab.
Medical campus fertile ground for success
With the experience and expertise on the CU Anschutz Medical Campus, the group is confident their efforts will have an impact. “We’ve done laboratory tests before and know how to get them to validation,” Frazer-Abel said. “And we have some really exciting ideas.”
“This is also potentially scalable at a completely different level than when basing what you are doing on one commercial kit,” Aisner said. “We could build the capacity to test hundreds of thousands of people with this across multiple labs.”
Liping’s lab has been developing autoantigen tests for autoimmune diseases for 30 years, pumping out 200,000 Type 1 diabetes tests annually. “So he is able to readily adapt that technique to test for coronavirus,” said Lori Sussel, PhD, BDC research director and part of the working group.
Liping, who uses the highly sensitive electrogenerated chemiluminescence (ECL) technology, said the campus SARS CoV-2 antibody test will be highly specific with a high-output capability. “One person in the lab can do thousands of samples a week.”
The campus effort becomes even more critical with the governor’s recent loosening of social-distancing mandates, Deane said. “And it gives the campus a great opportunity to not just work among ourselves, but to partner across the campus, community and state.”
Photo at top: Ashley Frazer-Abel, center, stands in her lab with her team, including: Dara Aisner, left; Brian Harry, right; and Thomas "Tem" Morrison, back.
