How Monoclonal Antibodies Might Prove Useful Against The Coronavirus

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When our bodies are invaded by a virus, our immune systems make particular proteins called antibodies to help fight off infection.

Scientists working to quell the COVID-19 pandemic think it will be possible to figure out which antibodies are most potent in quashing a coronavirus infection, and then make vast quantities of identical copies of these proteins synthetically.

This approach — using infusions of what are known as monoclonal antibodies – has already proved to be effective in fighting a variety of diseases, such as rheumatoid arthritis and some cancers.

Several efforts are underway to turn this approach on the coronavirus, with hopes of getting something ready for human testing within the next few months.

One such project, supported by the Defense Advanced Research Projects Agency, is called the Pandemic Prevention Platform. The idea is to shorten to just 90 days the time it takes to develop effective countermeasures to a biological threat like the coronavirus.

"I am happy to say that the clock has started," says DARPA's Amy Jenkins. "The clock started the first week of March."

The first step in the process is to identify the specific antibodies that recognize the new coronavirus.

The next step is to see if those antibodies can block the virus from infecting cells in the lab. Jenkins says that second step should be completed soon.

If the antibodies work to protect cells from infection, then researchers will test them in animals exposed to the virus — to see if the proteins prevent the animals from getting sick, or, alternatively, if they can improve the health of animals that are sick with a version of COVID-19.

Jenkins is concerned that the animal testing phase might take longer than she hopes. That's because researchers need special, genetically modified mice to test coronavirus therapies. Normal lab mice aren't easily infected with this virus, and the susceptible mice are in short supply.

So, Jenkins says, she and her colleagues are trying to find other animals they might use to develop their candidate antibody. For example, researchers in China have shown the rhesus monkeys can be infected with the new coronavirus, so that's one possibility.

"If the testing goes well and it shows efficacy in those animal models, our next step will be to start manufacturing," says Jenkins.

Best case scenario, she says, they might have a drug they can give to humans by June.

Under normal circumstances, even if experiments in animals showed the drug appeared to work and not cause any serious side effects, it would still require extensive testing in human before the FDA would approve it. But even that process may be streamlined if the pandemic significantly worsens.

Beyond the hunt for a good animal model, there's another big question mark hanging over the project at this point, Jenkins says: The antibodies her team is starting with in this case came from a single person who recovered from COVID-19. And there's a chance that person's antibodies aren't the most potent for neutralizing an infection.

"Doing this with just one patient is very, very risky," she says, but getting access to additional patients proved difficult at first, and Jenkins says her team was eager to get started.

Phil Pang, chief medical officer at Vir Biotechnology, is in the midst of a project he hopes will address that problem — his company is casting a much wider net.

"We are hoping to get up to 100 blood donors," Pang says, and they already have some promising candidates for antibodies to test. The company is still looking for volunteers who have recovered from COVID-19 and would like to donate a blood sample, he says.

"We believe that we are weeks — hopefully weeks,and certainly no more than months — away from identifying a highly potent monoclonal antibody," Pang says.

Meanwhile, the biotech company Regeneron thinks it has an even better way to develop antibodies — one that doesn't rely on humans at all. The company uses special mice that essentially have a human immune system. George Yancopoulos, Regeneron's chief scientific officer, says they already have hundreds of antibody candidates.

"And then, ultimately, we will choose the top two," Yancopoulos says. "We're hoping that by June we will have ... clinical grade material to start testing in human beings."

Yancopoulos says Regeneron has another drug — one already approved for treating rheumatoid arthritis — that may be useful in treating patients who have the pneumonia associated with COVID-19.

If that drug pans out against the COVID-19 pneumonia, Yancopoulos, says, it might one day be paired with an antibody drug as a combination treatment.

"We can be fighting the virus itself directly with these antibody cocktails while also fighting the inflammatory reaction that's harming the lungs," he says. "That might be a great double whammy."

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