New Valley fever vaccine for dogs is the first in the world to offer protection against a fungal disease
Dr. Lisa Shubitz and Marc Orbach didn’t set out to make a vaccine, much less the first vaccine of its kind in the world.
But that’s exactly what they did, thanks to Orbach’s connection with a corn geneticist, Shubitz’s lifelong passion for animals, a novel method of vaccine manufacturing and the fundraising efforts of a determined cadre of pet lovers.
Now, their team at the Valley Fever Center for Excellence at the University of Arizona has announced that their new vaccine is highly effective at protecting dogs against Valley fever. The vaccine, the researchers say, is the first to combat a fungal disease of any kind, a landmark step in vaccine research and genetics.
It’s also the most promising development yet in the long effort to prevent a mysterious and sometimes debilitating infection. The fungus that causes Valley fever lives in the soil in parts of California and the Southwest, including large swaths of Arizona. It affects both humans and dogs, and though it doesn’t induce symptoms in everyone, it can cause respiratory symptoms, joint pain and sometimes worse complications that can lead to serious illness or death.
The discovery of a vaccine is not only a relief to dog owners but also shows promise for developing a human vaccine, which researchers say now appears to be within reach.
“The research we do in general benefits both humans and animals in the end,” said Shubitz, a veterinarian and research scientist at the University of Arizona. “The idea that you worked on something that can help people's lives be better is very rewarding.”
While many scientists actively pursue useful drugs or products, Orbach described the vaccine as the exciting end result of a scientific process driven primarily by open-ended curiosity.
“When we do basic research, we always have this goal that our research will lead to something important for dealing with a disease,” said Orbach, a professor of plant pathology and microbiology at the University of Arizona. “It's beyond our wildest dreams that it actually worked.”
Part 1: Disarming Valley fever
Orbach wasn’t initially curious about humans or dogs or even mice. He was inspired by a friend’s research on corn, or more specifically, a fungus that attacks it.
Orbach’s friend, a researcher at Cornell named Gillian Turgeon, was telling him about her research on diseases that affect maize. Her team had found that they could alter a particular gene in a corn-targeting fungus to make it less harmful to the plant. Orbach wondered whether he could alter that gene in other types of fungus, like Coccidioides, which causes Valley fever.
“There are fungi that are specialized to infect plants, and fungi that are specialized to infect animals, but there are some genes that are conserved between (both),” Orbach said. “That's what (this) gene is one example of.”
So Orbach and his team set to work tweaking the DNA of the fungus. When they deleted the gene of interest, called cps-1, they realized that mice infected with the mutant fungus didn’t get sick.
They knew that they had created a disarmed version of Valley fever. But they weren’t sure whether it would actually create immunity.
For decades, the prospect of developing a vaccine against a fungal disease was a daunting one. That’s because the immune response in charge of neutralizing Valley fever is completely different from the response to other kinds of diseases.
When naturally infected with Valley fever, the body eventually finds ways to control the fungus without actually getting rid of it. That’s similar to what happens with the virus that causes chickenpox. But unlike most viruses — like SARS-CoV-2, for example, which is covered with many of the same “spike” protein — fungi have many types of proteins that the host can recognize. Researchers weren’t sure which of those proteins would actually be involved in creating an immune response.
But since Orbach’s innocuous version of Valley fever is exactly the same as regular Valley fever, just without the disease-causing part, it has all those proteins built in. That means they can induce a response similar to a natural infection without honing in on a single protein, which would be both technically difficult and more expensive to make, explained Dr. John Galgiani, a University of Arizona professor of medicine and director of the Valley Fever Center for Excellence.
“(The body) doesn't kill (the fungus that causes Valley fever). It just makes it go to sleep,” Galgiani said. “And we don't quite understand what ‘going to sleep’ is, which is a really interesting question.”
Still, said Galgiani, live vaccines like this one tend to be some of “the best vaccines in the world.” So they decided to test it on mice to see if it would work.
It did. Mice that had been previously given the mutant, harmless strain of Valley fever didn’t get sick when exposed to the disease-causing strain. “The results were so dramatic,” Galgiani said. “The vaccine looked so good, (even) on the first experiment...And the more we studied it, the better it looked.”
Part 2: Testing in dogs
In 1998, Shubitz’s dog, a whippet named Arrow, was diagnosed with Valley fever. It cost $10 a day for the medication to treat her, and even after three months, Arrow still had a persistent fever and signs of the disease in her lungs.
Eventually, they were able to find another medication that helped, but Shubitz said it was her personal experience of caring for a dog with Valley fever that inspired her to pursue the trials that would be needed to make a canine vaccine. “(Arrow) launched me into (studying canine Valley fever)...prior to that I was just doing mice,” said Shubitz.
But Shubitz’s interest wasn’t enough; her lab needed funding. That’s where the broader community came in.
“This is a vaccine that dog owners really enabled...they donated money for years and years,” Shubitz said. “Working with dog owners is really humbling. These people care so much about the disease in Arizona.”
Galgiani estimated that philanthropy from dog owners totaled about $200,000, which funded the preliminary research that ultimately led to a grant from the NIH and additional funding from the animal pharmaceutical company Anivive Lifesciences, based in Long Beach, Calif.
The dog trials paid off. All of the vaccinated dogs in the study either did not show any signs of illness or had such mild symptoms that they were clinically irrelevant.
Now, those results will pave the way for a vaccine that dog owners can actually use. “We think that it’s realistic that there will be a commercial vaccine for dogs available in the next year or so,” Orbach said.
Shubitz credits a bit of luck, and a lot of teamwork, for the success of the new vaccine. “A lot of science is serendipity followed by hard work,” she said. “(Science) isn’t work that was done by one person. This was done by lots of people that bring lots of kinds of expertise to bear.”
Part 3: ‘Spores in a bottle’
Galgiani said he was excited not only by the genetic technology that led to the discovery of the vaccine, but also by the feasibility of creating a financially viable end product.
“It’s spores in a bottle ... We just grow the spores and that's the vaccine,” Galgiani said.
That process is revolutionary in its own way, explained Dr. David Bruyette, chief medical officer at Anivive Lifesciences. Normally, Bruyette said, fungus is the last thing vaccine manufacturers want in a facility, because it’s considered a contaminant for viral or bacterial vaccines. So they had to create a new way to mass-produce and package the harmless Coccidioides spores.
After putting the right number of spores into a vial, manufacturers will deep freeze the vials in a special process that preserves the fungi without using water. That turns them into a powdery substance that a veterinarian can later turn into an injectable form using a saline solution.
“What you see within the vial ... it’s like a foam, it looks like cotton candy,” Bruyette said.
He added that the novel technology not only holds promise for eventually developing a human vaccine against Valley fever, but could also be extrapolated to develop other vaccines against diseases that affect pets across the country.
“There’s three big endemic fungi in the United States,” said Bruyette, who added that those species all cause pets to get sick. “And then there’s Cryptococcus (neoformans), (which is) a devastating disease worldwide.”
Galgiani said that people of color may be more susceptible to Valley fever than people of European descent due to complicated genetic factors, and Bruyette also noted that fungal diseases tend to make vulnerable populations the sickest, since immunocompromised individuals are least equipped to neutralize unwelcome fungi.
“I think that we're seeing a lot of interest from the US government in terms of funding more research into these diseases, and certainly (in) the idea of looking to create these different strains of fungus that don't make you sick but can stimulate your immune system,” Bruyette said.
The future: Humans and animals
In October 2019, Dena Olsen developed a cough that wouldn’t go away. She found it difficult to speak, or even sleep, without coughing. Her doctor tried a variety of treatments, but nothing seemed to work.
Then she took her dog in for an annual checkup, and her family veterinarian heard her cough. The vet told her she needed to be treated for Valley fever.
Olsen suggested the idea to her doctor, and four weeks into taking medicine for Valley fever, Olsen’s cough went away. Olsen credits her vet for the answers that healed her after months of exhaustion.
“Whether it’s an animal or a person, you have the same symptoms,” Olsen said. “It’s been very straining on me and my family.”
Even so, Olsen says she wouldn’t take a Valley fever vaccine if it was offered to her. “I don’t like putting foreign material in my body to prevent something from happening,” she said.
Jennifer Schaefer’s family has experienced a similar strain to Olsen’s, but Schaefer says she would be first in line for a human Valley fever vaccine someday. Her mother was diagnosed with Valley fever 20 years ago and spent a week in the hospital after developing pneumonia. Even now, she feels lingering effects, including what Schaefer describes as a “nasty cough.”
Then last fall, Schaefer’s English Mastiff Piper came down with Valley fever, too. They took Piper to a veterinary neurological center for seizures and had to keep up with over 20 pills a day when the illness was at its worst.
“It’s a long hard road,” Schaefer said. “(Dogs) can’t tell you what they’re feeling.”
She described the lack of preventative care for Valley fever as heart-wrenching and expressed excitement at the prospect of a canine vaccine on the horizon.
“Having this vaccine is unbelievable,” she said. “It could keep a lot of animals alive.”
Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.