Harvard Researchers Are Using a Breakthrough Tool to Find the Antibodies That Best Knock Out the Coronavirus

To find a cure for a deadly infectious disease in the 1995 medical thriller Outbreak, scientists extract the virus's antibodies from its original host—an African monkey.

"When a person is infected, the immune system makes antibodies kind of blindly."

The antibodies prevent the monkeys from getting sick, so doctors use these antibodies to make the therapeutic serum for humans. With SARS-CoV-2, the original hosts might be bats or pangolins, but scientists don't have access to either, so they are turning to the humans who beat the virus.

Patients who recovered from COVID-19 are valuable reservoirs of viral antibodies and may help scientists develop efficient therapeutics, says Stephen J. Elledge, professor of genetics and medicine at Harvard Medical School in Boston. Studying the structure of the antibodies floating in their blood can help understand what their immune systems did right to kill the pathogen.

When viruses invade the body, the immune system builds antibodies against them. The antibodies work like Velcro strips—they use special spots on their surface called paratopes to cling to the specific spots on the viral shell called epitopes. Once the antibodies circulating in the blood find their "match," they cling on to the virus and deactivate it.

But that process is far from simple. The epitopes and paratopes are built of various peptides that have complex shapes, are folded in specific ways, and may carry an electrical charge that repels certain molecules. Only when all of these parameters match, an antibody can get close enough to a viral particle—and shut it out.

So the immune system forges many different antibodies with varied parameters in hopes that some will work. "When a person is infected, the immune system makes antibodies kind of blindly," Elledge says. "It's doing a shotgun approach. It's not sure which ones will work, but it knows once it's made a good one that works."

Elledge and his team want to take the guessing out of the process. They are using their home-built tool VirScan to comb through the blood samples of the recovered COVID-19 patients to see what parameters the efficient antibodies should have. First developed in 2015, the VirScan has a library of epitopes found on the shells of viruses known to afflict humans, akin to a database of criminals' mug shots maintained by the police.

Originally, VirScan was meant to reveal which pathogens a person overcame throughout a lifetime, and could identify over 1,000 different strains of viruses and bacteria. When the team ran blood samples against the VirScan's library, the tool would pick out all the "usual suspects." And unlike traditional blood tests called ELISA, which can only detect one pathogen at a time, VirScan can detect all of them at once. Now, the team has updated VirScan with the SARS-CoV-2 "mug shot" and is beginning to test which antibodies from the recovered patients' blood will bind to them.

Knowing which antibodies bind best can also help fine-tune vaccines.

Obtaining blood samples was a challenge that caused some delays. "So far most of the recovered patients have been in China and those samples are hard to get," Elledge says. It also takes a person five to 10 days to develop antibodies, so the blood must be drawn at the right time during the illness. If a person is asymptomatic, it's hard to pinpoint the right moment. "We just got a couple of blood samples so we are testing now," he said. The team hopes to get some results very soon.

Elucidating the structure of efficient antibodies can help create therapeutics for COVID-19. "VirScan is a powerful technology to study antibody responses," says Harvard Medical School professor Dan Barouch, who also directs the Center for Virology and Vaccine Research. "A detailed understanding of the antibody responses to COVID-19 will help guide the design of next-generation vaccines and therapeutics."

For example, scientists can synthesize antibodies to specs and give them to patients as medicine. Once vaccines are designed, medics can use VirScan to see if those vaccinated again COVID-19 generate the necessary antibodies.

Knowing which antibodies bind best can also help fine-tune vaccines. Sometimes, viruses cause the immune system to generate antibodies that don't deactivate it. "We think the virus is trying to confuse the immune system; it is its business plan," Elledge says—so those unhelpful antibodies shouldn't be included in vaccines.

More importantly, VirScan can also tell which people have developed immunity to SARS-CoV-2 and can return to their workplaces and businesses, which is crucial to restoring the economy. Knowing one's immunity status is especially important for doctors working on the frontlines, Elledge notes. "The resistant ones can intubate the sick."