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How Regeneron Made a COVID Antibody Drug
It takes several weeks after infection or vaccination for the most effective antibodies to form in the human body.
Drugs like the one that scientists at Regeneron Pharmaceuticals developed are meant to help quickly. They supply strong doses of one or two antibodies that work well.
Drugs like these are being tested to prevent infection in people at high risk of COVID-19 who cannot yet get a vaccine, like those who live with COVID-19 patients. The drugs are also being tried as a treatment soon after infection to avoid serious illness.
They are some of the most complex medicines. Companies have used cells from different animals, such as monkeys, hamsters, mice, horses, cows and llamas to make them.
The antibody drugs start with one person who has had the coronavirus and recovered. Eli Lilly, for example, worked with AbCellera, a company in Canada that got a strong antibody from an early case in that country.
GlaxoSmithKline and Vir Biotechnology found one in blood that was frozen for years in a Swiss laboratory. It came from a person who had SARS, another coronavirus that caused a deadly outbreak in 2003.
Regeneron’s two-antibody drug is different. One antibody came from a person infected with COVID-19 in Singapore, the other from the company’s genetically modified mice.
Humans make hundreds or thousands of kinds of antibodies after infection. But “most of them are not very good” at blocking the coronavirus, said Christos Kyratsous. He is a microbiologist who helped lead Regeneron’s work.
The search began in January when Chinese scientists identified the new coronavirus. Dr. Sumathi Sivapalasingam started seeking blood samples from people who had been infected early in the health crisis. She is a Regeneron scientist who had worked at the U.S. Centers for Disease Control and Prevention.
Then, her team of researchers got a call from Dr. David Lye of Singapore’s National Center for Infectious Disease. Lye asked three of his patients who had recovered from COVID-19 pneumonia to give blood.
It was risky. Blood cells survive for around two days and the flight to New York takes 18 hours. The samples then would have to get through border control and be taken to Regeneron’s laboratory in Tarrytown, New York.
Dr. Lye was worried that a flight delay or any mistake during transport would make the blood useless.
It arrived on March 13, the day COVID-19 was declared a national emergency in the United States.
Other companies were working with mice that were modified to have human-like immune systems. When vaccinated with a piece of the virus, they do not get sick. Instead, they make almost the same antibodies humans make, Kyratsous said.
It takes just 20 to 30 of these mice to develop a drug. Blood from the mice and patients contains B cells. Each makes a special antibody that is carried on its surface. The goal is to find antibodies that stick to the virus and block it from infecting cells.
Scientists first check the B cells by mixing them with part of the spiky protein that covers the virus. They look for cells with antibodies that connect. Next, researchers examine the genetic material of each antibody. The genes are put into a kind of hamster cell widely used in the drug industry because it grows very quickly and produces the chosen antibody.
On Saturday, March 14, those are the results Kristen Pascal went to the lab to get. When the group saw good results, they celebrated. Those antibodies were just from the mice. Two weeks later, the process was repeated on the human samples from Singapore.
In its research, Regeneron tested more than 3,300 antibodies before choosing two that stuck to the spike protein at different places.
Dan Van Plew’s job is to take what he calls “the recipe” from the Tarrytown laboratory. He puts it through his “test kitchen” at Regeneron’s production factory in a nearby town. And he decides how to produce large amounts as a drug.
He said production took 45 days. That is “light speed” compared to the usual process that can take three to five months, Van Plew said.
In October, President Donald Trump received the drug himself. But there is no way to know if it helped. Most patients recover on their own and he received other experimental treatments, too.
The Food and Drug Administration has permitted use of Regeneron and Eli Lilly antibody drugs for moderately ill patients who do not need to be in the hospital. Tests on more severely sick, hospitalized patients were delayed because of concern that the drugs may not help.
I’m Alice Bryant.
The Associated Press reported this story. Alice Bryant adapted it for Learning English. Mario Ritter, Jr. was the editor.
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Words in This Story
dose –n. the amount of medicine needed to treat a disease
outbreak –n. the fast start and spread of a disease or of armed conflict
modify –v. to change a part of something while not changing other parts
pneumonia –n. a severe lung infection
spiky –adj. having sharp points
recipe –n. a set of instructions to make something (often food)