Monoclonal Antibodies May Prevent COVID-19 – But Effective Vaccines Complicate Their Future | Science

By Jon CohenJan. 22, 2021 at 16:20

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

A study in nursing homes in the United States has shown for the first time that monoclonal antibodies, mass-produced in the lab, can prevent people from developing symptomatic COVID-19. Their maker, Eli Lilly, hopes these antibodies will be another way to protect those at risk of serious illness from the pandemic coronavirus. But given the success of COVID-19 vaccines and their increasing availability, it is uncertain whether the expensive and somewhat cumbersome intervention will be widely used.

Eli Lilly’s monoclonal antibody and a two-antibody-like cocktail from Regeneron Pharmaceuticals – famous for treating former US President Donald Trump in October 2020 – have already received Emergency Use Clearance (EUA) as a therapeutic for those who have been infected and are at high risk of developing severe COVID-19. So far, they are not widely used as they need to be administered at the onset of infection and infused in a hospital or clinic. But now that they appear to be effective in preventing even mild illnesses, Eli Lilly is considering asking the U.S. Food and Drug Administration to expand the EUA to include preventative use.

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In the new study, nearly 1,000 people who lived or worked in nursing homes in the United States were given either a single infusion of Eli Lilly’s antibodies – containing four times the dose used therapeutically – or a placebo . In a press release yesterday, the company announced that the antibody reduced the risk of contracting COVID-19 by 57% within 8 weeks. Among residents of nursing homes, who made up about a third of trial participants, the risk of COVID-19 disease was reduced by 80%. Only four COVID-19–related deaths occurred in the study, and all were nursing home residents in the placebo group.

“I’m very happy with these results,” said Davey Smith, 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 nearly 40% of deaths from COVID-19 in the United States. “If this holds true, and I think there is every reason to believe it will, then that’s another tool,” says Rajesh Gandhi, infectious disease clinician at Massachusetts General Hospital. But he wants to see more specific data than that provided by the press release.

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

How Eli Lilly’s antibody would be used is not 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 who have only received one of the two vaccines. “It will probably be the niche population,” she says.

Myron Cohen of the University of North Carolina School of Medicine, one of the study’s lead investigators, says he hopes preventive doses could be given as easy-to-administer subcutaneous injections. , rather than infusions. Studies to test this strategy have started. Ideally, people infected with the virus should first be tested for antibodies against SARS-CoV-2, he adds: “People who already make antibodies probably don’t need them.”

Cohen adds that prevention and treatment trials have also had fundamental scientific payoffs: clarifying how antibodies prevent SARS-CoV-2 from causing serious illness. “Pretty much for the first time, I have a real understanding of the progression of the infection,” Cohen says.

The infection, he notes, starts in the nose and serious illness occurs when the virus reaches the lungs. Three days after an infected person received the monoclonal antibodies, Cohen said, the nasal swabs showed a “huge” drop in the levels of the virus in the nose, not seen in people given a placebo. This has led to better clinical results. Thus, the antibodies, whether administered as a preventive measure or as a treatment, seem to largely confine the infection to the nose.

One potential downside is that these monoclonal antibodies could interfere with the effectiveness of vaccines. The two vaccines licensed in the United States contain messenger RNA (mRNA) which directs the body’s cells to make the surface protein, the peak, of SARS-CoV-2, which then triggers the immune system to make antibodies. against the peak. The Eli Lilly and Regeneron monoclonal antibodies also target the spike, and the problem is, they could bind to the protein produced by the mRNA, stopping the dead vaccine in its tracks. Eli Lilly plans to start studies to test this in people who have been vaccinated, Sabo says.

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

But now that vaccines, cheaper and easier to administer, are being rolled out by the millions – with priority given to the most vulnerable populations – the question is what role remains for monoclonal drugs in the first place. Cohen says they could be important for the elderly and others with weakened immune systems who do not have vigorous responses to vaccines. “We just created integrated security,” he says. “If we never have to use it in the nursing home again, I’ll be happy.”