Jill Horowitz stood outside the Quaker Ridge Shopping Center in New Rochelle, N.Y.—an early COVID-19 hotspot—in March, stopping shoppers as they walked into the grocery store. She handed them blue pamphlets soliciting volunteers for a Rockefeller University antibody research study. “I would say, ‘Would you like to help us find a cure?’” says Horowitz, executive director of strategic operations at Rockefeller’s Laboratory of Molecular Immunology. “I didn’t even have to mention coronavirus. This neighborhood was completely subsumed.”
Within weeks—and after receiving more than 2,000 phone calls from volunteers—the university had selected more than 100 participants who had recovered from COVID-19 or had come into contact with someone who had the disease, says Michel Nussenzweig, head of the laboratory. From participants’ blood samples, he and his team isolated more than a dozen potent antibodies that “neutralized,” or deactivated, SARS-CoV-2, the virus that causes COVID-19, in a lab dish. The study is one of a growing number showing the body produces antibodies against this deadly disease. The findings suggest that therapies based on these proteins could be a promising approach. But experts caution that such therapies must clear several hurdles before they can be deployed against COVID-19.
Our body naturally produces antibodies to help us fight infections. Many researchers believe that by isolating antibodies from people who have recovered from COVID-19 and then artificially reproducing them, we can develop therapies that could minimize symptoms and speed recovery from the disease. Some of the same scientists are also eyeing the prophylactic use of copied antibodies to stave off an infection in those who have not contracted the new coronavirus. (Therapies based on these so-called monoclonal antibodies are different from convalescent plasma treatments, which have also made headlines recently. In the latter, plasma is taken from people who have recovered from COVID-19 and transfused directly into those who are infected. The jury is still out on whether convalescent plasma is truly effective against the disease.)
Historical precedent supports the use of antibody therapies: there are dozens of antibody-based drugs approved for various conditions in the U.S. or Europe, according to the Antibody Society, a nonprofit organization that tracks research on the proteins. These drugs are most commonly used to treat cancer and HIV infection, but a few have been utilized against respiratory infectious diseases. Notably, there is an antibody treatment that fights respiratory syncytial virus in children. And a more recent therapy that can help people with Ebola is now under review by the U.S. Food and Drug Administration. The treatment, called REGN-EB3, consists of three antibodies and was tested in a study during the Ebola outbreak that began in 2018 in the Democratic Republic of the Congo. That investigation showed that REGN-EB3 reduced mortality rates. The therapy was created by the Tarrytown, N.Y.–based biotechnology company Regeneron Pharmaceuticals, which is currently working on an antibody treatment for COVID-19.
Christos Kyratsous, vice president of research on infectious diseases and viral vector technologies at Regeneron, and his colleagues started developing antibodies against COVID-19 in January, when the genetic sequence for the disease was released. Using antibodies from genetically humanized mice—which carry functioning human genes—and people, Kyratsous has created an antibody cocktail that is set to enter clinical trials as early as June, he says. (In comparison, Horowitz says Rockefeller’s antibodies could begin clinical trials by August or September.)
Meanwhile Vanderbilt University researchers have collected antibodies from about a dozen of the earliest people in the U.S. to be infected with, and to recover from, COVID-19, says Robert Carnahan, associate director of the Vanderbilt Vaccine Center, who is leading the effort alongside James Crowe, the center’s director. In a preprint paper, Carnahan, Crowe and their colleagues reported they found about 40 potent antibodies against the novel coronavirus. The researchers are now working with multiple partners, including the Cambridge, England–based company AstraZeneca. Some of these partners are hoping to begin clinical trials of therapies using these antibodies as soon as this summer, Carnahan says.*
The studies from Rockefeller, Regeneron and Vanderbilt are just three among dozens with the same aim: finding antibodies that can help battle COVID-19. In the Netherlands, Erasmus Medical Center biologist Frank Grosveld and a team of researchers at Utrecht University and Harbour BioMed have isolated one antibody, called 47d11, that neutralizes SARS-CoV-2 and could be “developed at large scale,” he says. San Diego–based Sorrento Therapeutics has announced test results in a press release for the antibody STI-1499, which it plans to develop into a therapy. Eli Lilly, AbCellera, Distributed Bio and many other companies are also working on COVID-19 antibody therapies.
Even the most promising candidates are unlikely to be available before late this year, however. Clinical trials for therapeutics are smaller and faster than those for prophylactic treatments, and the FDA will probably approve the former quickly because “therapy is a dire need right now,” Horowitz says. Even so, such approval is expected to be at least six months away, she notes.
That time line coincides with the most ambitious estimates for when a vaccine could be available. On May 18 the Cambridge, Mass.–based company Moderna announced results from a clinical trial of a COVID-19 vaccine in a press release. The phase I trial (an early human trial that tests for safety) found that eight participants developed antibodies against the disease, Moderna says. The company has yet to release the trial data, however, and some scientists urge caution.
Moderna’s vaccine is one of more than 100 currently under development. Some scientists—including the company’s chief medical officer Tal Zaks—predict a vaccine could be available for widespread use later this year or in early 2021.
“Once we have a vaccine, there’s probably not going to be a strong need for these therapeutics anymore,” says Florian Krammer, a microbiologist and infectious disease expert at the Icahn School of Medicine at Mount Sinai. But Michael Joyner, a physiologist who is leading the Mayo Clinic’s convalescent plasma project for COVID-19, says antibody therapies could be a reasonable stopgap until a vaccine is available. “If they work and are used intelligently, [such therapies] could put a finger in a number of holes in the dike,” he says.
Some scientists are also concerned that drug manufacturers may not have the capacity to produce antibody therapies. “Every factory that gets built has a reason,” Horowitz says. “And you can bet that all those factories are committed to [existing] drugs that we need.”
Both good will and pharmaceutical industry interest in antibodies are in high supply, however, she says. “There are some aspirational aspects of [antibody drug production],” Horowitz admits, though the prospect is not out of the question. “I think everybody is stepping up to the plate.”
Another consideration is the fact that antibody therapies are most often given intravenously. It may be possible to deliver COVID-19 antibodies by injecting them under the skin, outside of a hospital setting. But Arthur Reingold, an epidemiologist and biostatistician at the University of California, Berkeley, warns that many low-income countries may not have the infrastructure in place to deliver such therapies via either route on a large scale. “These tend to be very expensive therapies,” he adds. Whereas vaccines can come with a two-digit out-of-pocket price tag for most consumers, antibody therapies can cost thousands of dollars, Reingold says.
These hurdles do not mean antibody therapies cannot aid in the fight against COVID-19. But the challenges should serve to temper our expectations, some experts say. “I think [researchers] should be careful about how they communicate and basically create hope in the population,” Krammer says. “I think it's very dangerous to say, ‘Within [months], we will have [an] antibody therapeutic that works, and everybody will get it.’ That’s unrealistic.”
*Editor’s Note (5/29/20): This sentence was edited after posting at Robert Carnahan’s request. The revision clarifies his comments about the time line for clinical trials of antibody therapies he is developing with AstraZeneca and other partners.