In late summer, as researchers accelerated the first clinical trials of COVID-19 vaccines for humans, a group of scientists in Colorado worked to inoculate a much more vulnerable species.
About 120 black-footed ferrets, one of the most endangered mammals in North America, were injected with an experimental COVID vaccine intended to protect the tiny, weasel-like creatures saved from extinction four decades ago.
The effort came months before U.S. Department of Agriculture officials began accepting applications from veterinary drug manufacturers for a commercial vaccine for minks, a close cousin of the ferrets. Farmed minks, bred for their valuable fur, have died by the tens of thousands in the US and culled by millions in Europe after contracting the COVID virus from infected people.
Vaccinating such vulnerable species against the disease is important not only for the animals, experts say, but potentially also for protecting people. Some of the most pernicious human diseases originated in animals, including the novel coronavirus, which is believed to have spread from bats to an intermediate species before leaping onto humans and causing the pandemic.
The concern when it comes to animals such as farmed minks, which are kept in crowded pens, is that the virus, contracted by humans, can mutate if it spreads quickly in the susceptible animals, and pose a new threat if it flows back to humans. Danish health officials reported in November that they had detected more than 200 COVID cases in humans with variants linked to farmed mink, including a dozen with a mutation that scientists feared would undermine vaccine effectiveness. However, officials now say that variant appears to be extinct.
In the US, scientists have not found similar COVID mutations in the domesticated farmed mink populations, although they have recently noted with concern that the first case of the virus has been detected in a wild mink in Utah.
“For highly contagious respiratory viruses, it’s very important to consider the animal reservoir,” says Dr. Corey Casper, a vaccinologist and chief executive of the Infectious Disease Research Institute in Seattle. “If the virus returns to the animal host and mutates, or changes, in a way that it can be reintroduced to humans, then the people no longer have that immunity. That worries me greatly.”
For the newly vaccinated ferrets, the greatest risk is for the animals themselves. They are part of a captive population at the National Black-footed Ferret Conservation Center outside Fort Collins, Colorado, where there have been no cases of COVID-19 to date. But the slender, furry creatures — known for their distinctive black eye mask, legs and feet — are feared to be highly vulnerable to the ravages of the disease, said Tonie Rocke, a research scientist at the National Wildlife Health Center who develops the ferret vaccine. They are all genetically similar, as they come from a small breeding ground, which weakens their immune system. And they probably share many of the characteristics that have made the disease so deadly for minks.
“We don’t have direct evidence that black-footed ferrets are susceptible to COVID-19, but given their close relationship to minks, we wouldn’t want to find out,” Rocke said.
Rocke began work on the experimental vaccine in the spring, while she and Pete Gober, black-footed ferret recovery coordinator for the U.S. Fish and Wildlife Service, followed reports of the novel coronavirus with growing alarm. An exotic disease is “the greatest nemesis for ferret recovery,” says Gober, who has worked with black-footed ferrets for 30 years. “It can take you right back to zero.”
Ferrets are a native species that once roamed vast tracts of the American West. Their ranks declined rapidly over many decades as prairie dog populations, the ferrets’ main source of food and shelter, were decimated by farming, grazing, and other human activities.
In 1979, black-footed ferrets were declared extinct — until a small population was discovered on a Wyoming ranch. Most of those rare animals were subsequently lost to disease, including the Sylvatic Plague, the animal version of the Black Death that has plagued humans. The species survived only because biologists saved 18 ferrets to form the basis of a captive breeding program, Gober said.
With the threat of a new disease looming, Gober doubled down on strict infection prevention precautions at the center, which houses more than half of the 300 black-footed ferrets in captivity. Another 400 have been reintroduced into the wild. Then he called Rocke, who had previously created a vaccine that has been shown to protect ferrets from the Sylvatic Plague. It uses a purified protein from Yersinia pestisthe bacteria that causes the disease.
Would the same technique work against the virus that causes COVID-19? Under the investigative powers granted by the Fish and Wildlife Service, the scientists were free to try.
“We can do things like this experimentally in animals that we can’t do in humans,” Rocke noted.
Rocke acquired purified protein of a key component of the SARS-CoV-2 virus, the spike protein, from a commercial manufacturer. She mixed the liquid protein with an adjuvant, a substance that boosts the immune response, and injected it under the animals’ skin.
The first doses were given in late spring to 18 black-footed ferrets, all males, all about a year old, followed by a booster dose a few weeks later. Within weeks of receiving the second injections, tests of the animals’ blood showed antibodies to the virus, a good — and expected — sign.
By early fall, 120 of the 180 ferrets housed at the center had been vaccinated, with the rest unvaccinated in case something went wrong with the animals, who generally live four to six years in captivity. So far, the vaccine seems safe, but there is no data yet to show whether it protects the animals from disease. “I can tell you we have no idea if it will work,” said Rocke, who plans to conduct efficacy tests this winter.
But Rocke’s effort makes sense, said Casper, who has created several vaccines for humans. Rocke’s approach — introducing an inactivated virus to an animal to boost an immune response — forms the basis for many common vaccines, such as those that prevent polio and flu.
Vaccines containing inactivated virus to prevent COVID-19 have been tested in certain animals — and in human vaccines, including CoronaVac, made by the Chinese company Sinovac Life Sciences. But efforts in Colorado may be among the first to target COVID-19 prevention in a specific animal population, Rocke said.
Gober said he is optimistic the ferrets will be protected, but it will take a well-designed study to resolve the issue. Until then, he will work to keep the vulnerable ferrets free from COVID-19. “The price of peace is eternal vigilance, they say. We must not be on our guard.”
The more difficult task is doing the same for humans, Gober noted.
“We’re just holding our breath, hoping we can get all the people in the country vaccinated. That will give us all a sigh of relief.”
Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.