The global search for a treatment targeting the novel coronavirus has led to an unlikely potential savior: a cocoa-colored llama named Winter, whose blood could hold a weapon to blunt the virus.
She lives at a research farm in Belgium with about 130 other llamas and alpacas. And like all of them, she produces a special class of disease-fighting antibodies — tiny, even by antibody standards — that show early promise in laboratory tests in blocking the novel coronavirus from entering and infecting cells.
In a paper published Tuesday in the journal Cell, an international team of scientists reports that these petite antibodies, harvested from Winter’s blood, were used to engineer a new antibody that binds to the spiky proteins that stud the surface of the novel coronavirus, “neutralizing” its insidious effect. The study, though preliminary, points to a possible treatment for COVID-19, the disease caused by the coronavirus, if the results hold up in animal and human studies.
Winter the llama is the cuddly face of a broader — and urgent — scientific quest to create coronavirus drugs inspired by the targeted responses mustered by the immune system. Winter’s antibodies are a niche kind that are called nanobodies and are prized by researchers because of their ability to get into nooks and crannies and because they are slow to degrade in the body.
Other scientists are exposing laboratory mice to the coronavirus spike protein and studying the blood of people who have recovered from COVID-19 to identify traditional antibody drugs. While work continues in the lab, U.S. hospitals are already harnessing naturally occurring antibodies to treat patients by providing experimental transfusions of blood plasma from COVID-19 survivors, hoping the plasma, rich with virus-fighting antibodies, can save lives.
With a widely available vaccine probably at least a year away, antibody therapies have become, in the eyes of some experts, one of the most promising weapons against COVID-19, which has killed more than 250,000 people worldwide.
Wayne Marasco, an infectious disease specialist at Dana-Farber Cancer Institute who developed experimental antibody therapies against close cousins of the current coronavirus, said he thinks the approach could be a “game changer.” A single dose could potentially act to treat the disease or to prevent it for months. Former Food and Drug Administration Commissioner Scott Gottlieb wrote in the Wall Street Journal last month that such drugs “may be the best chance for a meaningful near-term success.”
The antibodies inspired by Winter are still far from being tested in people. Belgian researchers are only now starting preclinical trials on hamsters.
But other efforts to create more-traditional antibody drugs are moving forward fast, with the hope they could provide a bridge until there is a vaccine.
Regeneron Pharmaceuticals exposed a special strain of mice, genetically tweaked to have a human immune system, to the characteristic spike protein on the surface of the coronavirus to identify thousands of antibodies that show promise. The company also studied the blood of people who recovered. The company will start several human trials in June, testing antibody cocktails both as a treatment and a prevention measure for people who are at high-risk of developing COVID-19. The company hopes to make the treatment available by the end of summer or early fall, with the ability to manufacture hundreds of thousands of doses.
“It’s never been done before,” George Yancopoulos, chief scientific officer of Regeneron, told investors Tuesday. “On the other hand, I don’t think we ever had quite a pandemic like this before … And so the hope is yes, it might be possible by the end of the summer or the fall that, our antibody treatment could be available. A lot of risks, a lot of concerns, but we are working as hard as we can with so many collaborators to try to turn that into a reality.”
Vir Biotechnology, which also plans to start human tests this summer, hired a nationwide network of phlebotomists to go door-to-door collecting blood from people who recovered from COVID-19 to aid the search for an antibody-based treatment. The company that did the blood draws, Sanguine Biosciences, sent phlebotomists to people at home to reduce the risk of infection, saving recently recovered people a trip to a crowded clinic or laboratory.
A research team from Utrecht University in the Netherlands reported Monday in the journal Nature Communications that it had created a monoclonal antibody called 47D11 that is capable of blocking the coronavirus in laboratory tests.
Such drugs are manufactured not by chemists but by living cells growing in bioreactor vats and tend to be expensive; they must be given by injection. Even now, with little idea of whether their drugs will be shown safe and effective, researchers are thinking about how to increase production.
“It takes time to scale, and we’re already scaling,” said George Scangos, chief executive of Vir. “The problem with this whole approach is you have to scale before you know if your drug works. Because if you don’t [scale], and your drug works — now it’s a year before you can provide any reasonable number of doses, and that’s not a situation that anyone wants to be in.”
The fastest way to a coronavirus treatment would be to repurpose an existing drug with a long safety record. To that end, scientists are pulling many time-tested drugs off the shelf to see whether they show promise in laboratory experiments and are moving some into the clinic. But antibody treatments could provide a powerful and targeted way to quickly develop a new drug that not only treats the disease but also could prevent people from becoming ill.
Much of this research already has a head start based on experience with severe acute respiratory syndrome (SARS). Marasco developed a library of 27 billion human antibodies from blood samples taken from hospital staffers in the late 1990s, which he then used to develop experimental therapies for SARS and Middle East respiratory syndrome (MERS). Those therapies were licensed to companies, but government and commercial interest evaporated when those viral outbreaks petered out. Marasco is working now on antibody therapies for the novel coronavirus, confident that this time things will be different.
Winter’s part in the battle against coronavirus disease began in 2016, when researchers immunized her with spike proteins from MERS and SARS. Then they drew her blood and isolated antibodies, one of which showed potential for neutralizing MERS, and another of which neutralized SARS, said Daniel Wrapp, a co-author of the study and graduate student at the University of Texas at Austin.
The Texas team, working with colleagues at the U.S. National Institutes of Health and Ghent University in Belgium, was trying to develop a universal vaccine for human coronaviruses, four of which are common and cause cold-like symptoms. While the researchers were hoping to find a single antibody that could target all the coronaviruses, the “consolation prize” was finding two that showed promise against MERS and SARS, Wrapp said.
They were writing up what they’d learned from Winter when the novel coronavirus emerged. They quickly got to work. Soon, they’d found that a new antibody — which they created by linking two copies of the llama antibody that had hindered the original SARS — was able to bind to and neutralize the novel coronavirus, known as SARS-CoV-2, Wrapp said.
“It’s interesting to have a renewed sense of urgency toward your work, because it could have such dramatic implications for vaccine development and therapeutic” treatments, Wrapp said.
If the small antibodies work in humans, their stability means they possibly could be delivered as treatment via an inhaler, Wrapp said. Larger monoclonal antibodies must be administered by injection.
Winter was randomly selected from her herd to participate in this research, noted Wrapp, who has never met the 4-year-old llama. Now, he said, “she’s kind of the superstar of this.”