Universities band together to develop S.C.-grown antibody test

April 27, 2020
A woman in a blue paper gown and gloves stands in a room of massive gray machines
MUSC clinical laboratory scientist Elizabeth Champion-Lyons sets up the i2000SR Architect Plus Immunoassay machine for calibration in preparation for antibody testing. Photos by Sarah Pack

A statewide collaboration among South Carolina’s research universities and largest health systems is setting the stage for widespread availability of coronavirus antibody testing, a key component of a strategy for safely reopening the state. 

David Cole, M.D., FACS, president of the Medical University of South Carolina, has said there are five essential elements necessary to allow everyone to get to a “new normal”: economic revitalization; diagnostic testing for COVID-19, the disease caused by this new coronavirus; antibody testing for SARS-CoV-2, the specific form of coronavirus that caused the pandemic; contact tracing; and protection of vulnerable populations.

MUSC has been working alongside Clemson University and the University of South Carolina, as well as Prisma Health, for the past month to develop reliable antibody tests. Antibody testing, along with diagnostic testing, would together provide policymakers with valuable information about the present state of infections once commerce recommences so they can determine what, if any, real-time measures might be necessary.

MUSC Health will begin offering antibody testing to its workforce today, and the three universities hope to scale up testing quickly to be able to offer it to all health care workers in the state and, this summer, to the community at large.

As the pandemic took hold, MUSC decided on a dual approach to securing antibody tests. It would buy tests developed commercially, but it would also work on creating its own so it could be self-reliant.

“Early on in this coronavirus pandemic, we realized in all kinds of ways our supply chains were being interrupted. Most of the supply chain interruptions were either from consumption – other places trying to do the same thing we’re trying to do – or from true disruption in the supply chain,” said Danielle Bowen Scheurer, M.D., chief quality officer for the MUSC Health system. “For example, many of our medical supplies come from China, Singapore and places that were hard hit to begin with, so production went down, and consumption went up.

“We've learned the hard way that any one product line can literally be shut off in a matter of hours,” she said.

The hospital system was able to buy antibody tests from Abbott Laboratories. The Department of Pathology and Laboratory Medicine validated them, and these tests are now ready to roll out.

At the same time, scientists at each of the three universities have been racing to build a test. Each university has its own core competency, and the three have been able to complement each other, Scheurer said.

Labs at the three universities started off by working with plasmid, or DNA molecules, that expressed SARS-CoV-2 proteins. The plasmid was obtained by Clemson University from Mount Sinai Laboratory, which on April 15 announced it had received emergency-use authorization for an antibody test it developed. As each university works on developing a test and growing its own proteins, they’re cross-checking each other’s work and using patient samples from MUSC Health and Prisma Health to validate their results.

“This highlights the importance of research in a medical institute. Having both the basic science component and the clinical component together in an institute like MUSC is an advantage to us.”
Shikhar Mehrotra, Ph.D.
associate scientific director, Center for Cellular Therapy

At MUSC, Satish Nadig, M.D., D.Phil., medical director of the Center for Cellular Therapy, got a call from Cole a few weeks ago asking him to get a group together to start working on an in-house antibody test. 

The first person he called was Shikhar Mehrotra, Ph.D., associate scientific director of the MUSC Center for Cellular Therapy. Then they brought in MUSC colleagues Stephen Tomlinson, Ph.D., interim chairman of the Department of Microbiology and Immunology, and Philip Howe, Ph.D., chairman of the Department of Biochemistry, forming a truly interdisciplinary group.

“The word interdisciplinary is often a buzzword that is in vogue, but this group showed what it looked like in action,” Nadig said.

The group took a two-pronged approach. Howe and Tomlinson would work on growing proteins, using the Mount Sinai plasmids, while Carsten Krieg, Ph.D., an assistant professor in the Department of Microbiology and Immunology, would purchase proteins that recently had become commercially available. The team, with the Center for Cellular Therapy leading, would then develop and validate tests with each, first using control antibodies, then using patient samples available through the convalescent plasma program led by John Wrangle, M.D., and a biorepository overseen by Patrick Flume, M.D.

“This highlights the importance of research in a medical institute. Having both the basic science component and the clinical component together in an institute like MUSC is an advantage to us,” Mehrotra said.

A man in a white lab coat sits at a table and pipettes samples behind a transparent shield 
Carsten Krieg, Ph.D., in his lab. 

Many of the scientists pivoted from their regular research to concentrate on the antibody project, putting in nights and weekends as they compared notes across the state. Phil Buckhaults, Ph.D., an associate professor in the College of Pharmacy at the University of South Carolina, typically focuses on cancer genomics – figuring out cancer mutations and how to kill cancer cells. He doesn’t have a background in epidemiology or infectious diseases, he said, but he has skills that are useful – namely, his lab is skilled in high-throughput sequencing, which should enable them to eventually run tests for 20,000 people a day.

The three universities have ongoing partnerships in a variety of areas, but this effort feels different to all involved. Buckhaults points to how scientists from the three institutions are sharing their problems and solutions with each other in regular video calls and emails in a refreshing break from typical academic competition. It feels like he’s been dropped in the middle of a forest fire and, though everyone is wearing different uniforms, they’re all passing buckets of water and chopping down trees together as fast as they can, he said.

“It took something like this to scare the bejesus out of everybody,” he said.

And he thinks it’s smart for the universities to work together to ensure that the people of South Carolina have access to these tests.

“We’re not waiting on somewhere else to solve the problem for us,” he said.

Delphine Dean, Ph.D., a professor in Clemson University’s Department of Bioengineering, is leading Clemson’s multidepartmental effort. Clemson is working on two approaches at once, she said. It’s working to scale up the number of blood-based antibody tests that it can produce, but it’s also working to develop a point-of-care test that could use saliva or urine and would show a result in much the same way a pregnancy test does. But, she said, “The concentration of these antibodies in saliva is 1,000 times less than in blood,” she said.

It’s unusual to be developing both of these tests at once, she said. But then, it’s unusual for the researchers at the three universities to be communicating daily so closely.

“One of the things that’s exciting is that, A., we’re all working together – it’s unprecedented. We're working very fast to break down all the institutional barriers. The other thing is we’re doing this very quantitative lab-based test and validation at the same time that we’re developing the next level point-of-care fast test,” she said.

MUSC scientists paused their regular work to jump into the project without hesitation. Tomlinson said his research already involves expressing and purifying proteins. “It was a quick and easy switch for us to change over to producing SARS-CoV-2 proteins. We successfully produced the proteins in a pilot study, but since the proteins have become commercially available, we halted further production.”

Using the commercial protein has proved more cost effective, Nadig said, adding that it’s good to have in-house capabilities as a backup plan.

“That was a good move in terms of, ‘Now we can be confident we can keep on going no matter what,’ instead of depending on commercially available protein,” Mehrotra agreed.

Nadig credited Mehrotra and Colleen Cloud, operations manager for the Center for Cellular Therapy, for making the project happen in record-breaking time, and the entire interdisciplinary team for stepping up.

“In three weeks, from being tasked with the operation of having an in-house assay to the final product, the clean cell facility was able to produce. It's been a whole can-do attitude to do this. It really shows an interdisciplinary perspective on the capability that MUSC has to get things done,” Nadig said.

"It's been a whole can-do attitude to do this. It really shows an interdisciplinary perspective on the capability that MUSC has to get things done." 
Satish Nadig, M.D., D.Phil.
medical director, Center for Cellular Therapy

MUSC will first make the Abbott tests available to its workers who have patient contact. That includes not just those involved in direct patient care but also groups like security and facilities who are around patients, Scheurer said. Once the home-grown tests are validated and the three universities have sufficient quantities, it will make tests available to first responders and health care workers throughout the state, then to the broader community. 

But, Scheurer cautioned, scientists are still figuring out what the results of those tests mean, on a practical level. A person may show SARS-CoV-2 antibodies, but we don’t yet know how much protection those antibodies confer or how long the protection will last, she said.

“We're not recommending that health care workers make work choices based on the results,” she said, while also noting that the tests are voluntary and confidential – supervisors will not have access to the results. But she thinks the results could give peace of mind to health care workers who are concerned they might bring the disease home to their families.

“It gives them some reassurance that they probably have been exposed, and they have mounted some protective response, but we don’t want them taking that leap of faith to say, ‘I don’t need protective equipment. I don’t need a face shield or a mask when taking care of a COVID patient,’ or ‘I have free rein from a social distancing perspective,’” she said.

The bigger questions are for policymakers. Scheurer hopes that widespread antibody testing will start to give leaders better information with which to make decisions, for example, determining what percentage of people have at least some antibodies. She suspects that number will be low, though. After all, of those who went through the virtual care screening and qualified to receive a COVID-19 test, only about 6% have tested positive – and these are all people who had symptoms, she said. But knowing how prevalent this coronavirus is should help leaders to figure out how to approach decisions and to help people support social distancing measures.

“All these things we’re enduring are really life changing and very difficult to sustain – up to and including having school canceled. If people are going to make a medium- or long-term sacrifice, it’s got to be because they truly understand what we’re up against,” she said.

There are people who are truly suffering because of the measures that have had to be instituted, she said.

“When you think about nursing home patients right how who have not had any contact with anyone other than their nurses for a month or longer – and there’s no end in sight for them – those are real sacrifices that are going to be incredibly difficult to sustain for long periods of time.”

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