Last week, gorillas and orangutans at New Orleans’ Audubon Zoo saddled up to a fence in their enclosure to receive their first doses of a COVID-19 vaccine for animals.
Audubon is one of around 80 zoos across the US that have asked for experimental doses of the vaccine, says Mahesh Kumar, head of vaccine research for Zoetis, which manufactures the animal vaccine. In Louisiana, one of the first COVID shots for animals went to Mike the tiger, the mascot of Louisiana State University, who was vaccinated back in August. This past weekend, the National Zoo in Washington, D.C. started immunizing its primates.
Throughout the pandemic, zoos have been sites of COVID outbreaks—during New York City’s first wave last spring, four Malayan tigers and three African lions tested positive for COVID at the city’s Bronx Zoo. There have also been outbreaks in primates, and mustelids—members of the weasel family, like otters and ferrets—are known to be susceptible. Most animals recovered, although in the past week, a North Dakota snow leopard and a Hawaii lion both died of COVID.
Bob MacLean, Audubon’s senior veterinarian, says that they haven’t had any documented COVID cases at the zoo. But across the country, zoo animals have lived under many of the same COVID precautions as the rest of us, often involving social distancing and restricted visitors.
Delivering shots to zoo animals is a little different from administering vaccines to humans. First, zookeepers convince the animal to lean against a mesh barrier. For the gorillas and other primates, this is a lot like leaning against a wall. Cats and mustelids may have to sit on a carefully placed log. Once they’re comfortable there, the keepers begin desensitizing them to the poke, giving them treats while they tap them first with a popsicle stick, then a dull needle, and finally an injection.
From there, the process is much like human vaccines: two shots, 21 days apart. The zoo is vaccinating 10 primates to begin with, and plans to follow with 60 more doses for big cats and mustelids. That’s the plan at most zoos nationally. And while it’s not unusual to give animals some routine shots, MacLean says the zoo hasn’t run a similar mass vaccination campaign since West Nile Virus, a mosquito-borne disease, began spreading in the early 2000s.
So far, the Audubon Zoo hasn’t seen any side effects, MacLean says, except that “keepers think the gorillas may have some arm soreness.”
Wait, we already have an animal vaccine?
The COVID vaccines for humans were developed in record time, surpassing many of the most optimistic predictions from early in the pandemic. So it might seem surprising that a drug company has put out an animal vaccine at nearly the same pace.
But it shouldn’t: Animal coronavirus vaccines have actually been around since the 1950s, says Linda Saif, a virologist at the Ohio State University, who has studied and developed coronavirus vaccines for decades.
Pigs, cows, chickens, and even cats and dogs are susceptible to other coronaviruses, sometimes with devastating consequences. A chicken coronavirus can affect the reproductive system of hens, causing them to stop laying eggs. Another affects cattle, resulting in everything from diarrhea in calves to respiratory infections in feedlot cattle. And in the early 2000s, a virulent strain of a pig coronavirus swept across the US, killing millions of piglets.
The first chicken coronavirus vaccines were developed as far back as the 1950s, Saif says, although the technology has evolved since. “The major problem is the variants,” she says. Every few years, they have to create new vaccines.
Even though vaccines exist for a range of animal coronaviruses, “they’re very specific,” says Kumar. “Every coronavirus has to be protected by its own vaccine.”
But the existing technology did give Zoetis a running start. Their COVID-19 vaccine uses purified SARS-CoV-2 spike proteins, called S-Trimers—to provoke an immune response. That’s the same underlying technology as other animal coronavirus vaccines. (It’s also similar to the Novavax shot for humans.) “We know that if you take this little key piece and make that into a vaccine,” says Kumar, “it will work for that specific coronavirus.”
Zoetis initially began researching the COVID vaccine in cats and dogs in 2020, after two dogs caught coronavirus from their owners in Hong Kong. But, Kumar says, the USDA, which licenses veterinary vaccines, said that the risk to pets was too low to support a license, so the company put the drug on hold.
But then came the news that minks, which are farmed for fur, could be infected—and in some cases, could transmit COVID-19 back to humans. Now, Zoetis is testing the vaccine in minks in order to get a provisional license from the USDA, roughly equivalent to an animal emergency use authorization.
The end goal is still to have the vaccine on hand for cats and dogs, but Kumar says that the San Diego Zoo heard about the trial after its gorillas had an outbreak, likely via an infected zookeeper. “They came to us and said, listen, we’re having problems in primates. We sent them a vaccine that we’d developed, and they spread the word, and we were bombarded with requests.”
Right now, the vaccine is being administered as an experimental treatment in advance of the licensing process. But licensing a vaccine for an entire zoo would pose a huge hurdle.
“I remember facing this problem when we were working on the bird flu vaccine,” says Kumar. “Some of the zoos wanted to use that vaccine, and we asked the government, how can we get approval? They said we had to get data for every species of bird we want to use it in. I asked the question, do you know how many bird species there are in the world? It’s impossible to make a product for every species.”
One of the main differences among vaccines for new species is the choice of adjuvant, which is the compound added to the viral material to help stimulate the body’s immune system. Some adjuvants slowly release viral material over time, prolonging the immune response. Others act like a beacon to the immune system, provoking a more intense reaction. But they can trigger allergic reactions or other side effects in different species.
In order to give their shot to everything from monkeys to otters—by Zoetis’ count, more than 100 species—Kumar says they used an adjuvant that they’re confident is safe across the board. And they’re giving two shots, hoping that it will create some degree of immune response in all kinds of species.
Kumar readily acknowledges that it’s not clear how well the vaccines will work across species.
“We have no real data in zoo animals,” Kumar says. But he notes that “we know that there hasn’t been a single [mink] outbreak after the vaccine. We feel that anecdotally it’s been effective in the field.”
The company isn’t ready to release efficacy data from its ongoing trial in minks, but results in cats and dogs presented at a conference last year showed that two doses of the drug boosted antibody levels after about a month.
Saif says that based on her experience developing a vaccine for the deadly pig coronavirus, the technology used for Zoetis’ vaccine only stopped transmission altogether “if the sow was first naturally infected” or given a vaccine that included live virus. “Then the spike vaccine worked as a booster.” Two rounds of the same kind of vaccine might not be as effective. Still, as we’ve seen in humans, the vaccine doesn’t need to completely stop transmission to be life-changing.