Monoclonal antibodies can prevent COVID-19—but successful vaccines complicate their future

Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

A study in U.S. nursing homes has shown for the first time that monoclonal antibodies, mass-produced in a laboratory, can protect people from developing symptomatic COVID-19. Their manufacturer, Eli Lilly, hopes these antibodies will provide an additional way to protect people at risk of serious disease from the pandemic coronavirus. But given the success of COVID-19 vaccines and their increasing availability, it’s not clear that the expensive and somewhat cumbersome intervention will be widely used.

Both Eli Lilly’s monoclonal antibody and a similar two-antibody cocktail from Regeneron Pharmaceuticals—famously used to treat former U.S. President Donald Trump in October 2020—have already received emergency use authorization (EUA) as a therapeutic for those who have become infected and are at high risk of developing severe COVID-19. So far, they are not widely used because they must be given early in infection and infused in a hospital or clinic. But now that they appear effective at preventing even mild disease, Eli Lilly plans to ask the U.S. Food and Drug Administration to expand the EUA to include use as a preventive.

In the new study, nearly 1000 people who lived or worked in U.S. nursing homes received either a single infusion of Eli Lilly’s antibody—containing four times the dose used for therapeutic purposes—or a placebo. In a press release yesterday, the company announced that the antibody reduced the risk of becoming ill with COVID-19 in the following 8 weeks by 57%. Among nursing home residents, who made up about one-third of the trial participants, the risk of COVID-19 illness dropped by 80%. Only four COVID-19–related deaths occurred in the study, and all were in nursing home residents in the placebo group.

“I’m superhappy about these results,” says Davey Smith, an infectious disease clinician at the University of California, San Diego, who was not involved in the study. He says the antibodies could be “really helpful” in long-term care facilities, which account for almost 40% of U.S. COVID-19 deaths. “If this is borne out, and I think there’s every reason to think it will be, then it’s another tool,” says Rajesh Gandhi, an infectious disease clinician at Massachusetts General Hospital. But he wants to see more specific data than the press release provides.

The finding that the antibody worked better in nursing home residents than staff may seem puzzling—and indeed the press release leaves out details that statisticians contacted by Science said they needed to make sense of this. But Eli Lilly’s Janelle Sabo explains the study measured reductions in risk, and residents have a higher risk of developing symptomatic COVID-19: They’re older and often have weaker immune systems and more underlying diseases, and they never leave. Staff spend less time at the facilities and can stay home if there is an outbreak, she says. “What we find then, of course, is there’s more opportunity to reduce the risk of infection [among residents] than in the overall population,” says Sabo, a pharmacologist.

How Eli Lilly’s antibody would be used isn’t entirely clear. Sabo suggests that if an outbreak occurs in a nursing facility, it could be given to residents who have not been vaccinated or have only received one of the two shots. “That’s probably going to be the niche population,” she says.

Myron Cohen of the University of North Carolina School of Medicine, one of the study’s principal investigators, says he hopes preventive doses could be given as easy-to-administer subcutaneous shots, rather than infusions. Studies to test that strategy have begun. Ideally, those infected with the virus should receive a SARS-CoV-2 antibody test first, he adds: “People already making antibodies probably don’t need this.”

Cohen adds that the prevention and treatment trials have also had a basic science payoff: clarifying how antibodies prevent SARS-CoV-2 from causing serious disease. “Pretty much for the first time I have a real grasp of how the infection progresses,” Cohen says.

Infection, he notes, begins in the nose, and severe disease occurs when the virus reaches the lungs. Three days after an infected person received the monoclonal antibodies, Cohen says, nose swabs showed a “huge” drop in virus levels in the nose, not seen in people who received a placebo. That, in turn, led to better clinical outcomes. So, the antibodies, whether given as preventive or treatment, appear to largely confine the infection to the nose.

One potential drawback is that these monoclonal antibodies could undermine the effectiveness of vaccines. The two vaccines authorized in the United States contain messenger RNA (mRNA) that directs the body’s cells to make the surface protein, spike, of SARS-CoV-2, which then triggers the immune system to make antibodies against spike. The Eli Lilly and Regeneron monoclonal antibodies also target spike, and the concern is that they could bind to the protein made by the mRNA, stopping the vaccine dead in its tracks. Eli Lilly plans to launch studies to test this in vaccinated people, Sabo says.

Monoclonal antibodies could also lose their potency because of viral mutations. One study of a SARS-CoV-2 mutant circulating widely in South Africa, published 19 January on the preprint server bioRxiv, has already shown this in test tube experiments.

But now that vaccines, cheaper and easier to administer, are being deployed by the millions—with priority for the most vulnerable populations—the question is what role remains for monoclonals in the first place. Cohen says they might be important for the elderly and other people with compromised immune systems who do not have vigorous responses to vaccines. “We’ve just created a failsafe,” he says. “If we never have to use it in the nursing home again, I’ll be thrilled.”