“May I Borrow Your Covid Immunity?”
[Print Title: “Resistance”]
WIRED, January 20, 2021
By Roxanne Khamsi
“Whenever a new virus emerges—be it HIV or SARS-CoV-2—a few lucky people put up a potent natural defense. Monoclonal antibody drugs let them share the health.”
A year ago, in January, when John Mascola heard that a new coronavirus had been detected in an animal market in Wuhan, China, he left everything at his desk on the fourth floor of the US government’s Vaccine Research Center and walked up one flight of stairs to the office of a longtime colleague, Nicole Doria-Rose. Felicitously, Mascola, who is the center’s director, had been working on ways to immunize people against coronaviruses. A vaccine against this new bug, soon to be known as SARS-CoV-2, was the first priority, the only surefire way of halting the growing pandemic. Mascola and Doria-Rose, an immunologist, go way back. And they hoped there was another approach that might also contribute to the cause, one they’d been chasing for more than a decade. They wanted to find a monoclonal antibody.
Everybody knows about vaccines, which train the immune system to fight invaders, but monoclonal antibody drugs are less familiar. To develop them, scientists must generally find a person whose body has done better than most at fighting a disease; scour their immune system, needle-in-a-haystack style, to locate the most effective antibody; and use it as a blueprint to fashion a drug for people who are sick. When former New Jersey governor Chris Christie came down with Covid-19 in early October, he was given an experimental monoclonal antibody drug made by Eli Lilly. That treatment—with the exceedingly unpronounceable name bamlanivimab—can be traced directly back to the conversation Mascola had with Doria-Rose at the start of the pandemic. The Food and Drug Administration approved it for emergency use on November 9. Similarly, a combination of two other antibody drugs, made by the company Regeneron, was given to then-president Donald Trump when he contracted the virus. Like the vaccines made by Pfizer and Moderna, these monoclonals were deployed in record time.
Mascola became interested in monoclonal antibody treatments in the early 2000s, not long after he joined the Vaccine Research Center in Bethesda, Maryland. Back then, if you studied infectious diseases, as Mascola did, you were probably trying to understand HIV. It had killed an estimated 22 million people and seemed unstoppable. HIV wasn’t as easy to contract as a respiratory illness—bodily fluids such as blood or semen, not the air you breathe, are the media for transmission—but once the virus took hold, its passage through the body was relentless. Patients suffered an array of painful symptoms, including mouth ulcers, skin sores, and pneumonia, before succumbing to a total collapse of the body’s defenses. But there was a small percentage of people who held out longer; they made stronger antibodies against the virus.
Other researchers had shown it was possible to isolate one of those superpowered antibodies, and starting in 2006, Doria-Rose joined Mascola in setting out to catalog the immune systems of exceptional HIV fighters. They first had to find HIV patients who had been infected for years but had remained relatively healthy; then, from each of those people, they had to collect and analyze samples of blood to know if the donors were among the estimated 1 percent of people with the virus who made highly effective antibodies. The blood was processed through machines that quickly separated out antibody-producing cells, called B cells, which were then deposited into the tiny wells of a tray resembling a Keebler elf’s muffin tin. From there, Mascola’s team would capture the antibodies produced by each cell cocooned in the individual wells.
Next, they tested the antibodies for strength. They took a line of specially engineered human cells, designed to glow green when infected with an HIV-like virus, and bathed them in antibodies. Then they exposed the cells to the virus. If the antibody was a dud, the infected cells would glow; if it had superpowers, they wouldn’t. Most of the time the mixture glowed. This went on for months; hundreds of samples failed.
But one day in 2009, while Mascola was sitting in the laboratory break room about to eat a sandwich, one of his scientists bounded toward him with a big smile on her face: They’d found the no-glow they’d been looking for.
That antibody came from a man known as Donor 45. Doria-Rose, who met with study participants when they came in for their regular checkups, says that Donor 45 was an exceedingly private gay Black man in his sixties from the Washington, DC, area. They dubbed the antibody VRC01—the first from the Vaccine Research Center.
It took almost a decade to develop a drug from this antibody and set up a clinical trial to make sure it was safe and effective. Other HIV researchers going down different roads came up with anti-retroviral drugs—the famous “triple cocktail”—that effectively treat and prevent HIV infections by interfering with the virus’s ability to make copies of itself. The crisis wasn’t over. People still contracted HIV, but with the antiretrovirals they could live mostly normal lives. As access to those drugs expanded, the effort to use antibodies to make HIV drugs became less urgent. It plugged along, a clinical trial was started, but not as many people were paying much attention.
And then came Covid-19. That day in January 2020, Mascola immediately saw that everything he and his colleagues had learned from studying HIV antibodies could be mobilized to treat the new pathogen. It would be “the culmination of a life’s work,” he says.
About the Author:
Roxanne Khamsi is a science writer living in Montreal.