Randy Ford had never heard of valley fever when he moved to Tucson from Salinas with his dog, a reddish brown vizsla named Tyler.
“A few days before Tyler’s death, he was doing hell – chasing toys in the pool. Then all of a sudden he stopped eating, and he was standing in front of his dog’s door and was shaking like he was. it was cold, ”Ford said.
That was in 2005. Tyler had breathed in spores from the fungus that causes valley fever, a disease that starts in the lungs and can then spread. The Tyler Valley fever infection had spread to his bloodstream and his kidneys began to shut down. Ford spent over $ 5,000 trying to save his beloved dog, but Tyler was too sick. He died a few days after his first illness.
An annual Howliday Party in Tyler’s memory has been held every year since his death at Tucson’s Sit! Stay! Play! Dog daycare, where Tyler was a client.
The event raises between $ 2,000 and $ 4,000 per year for the University of Arizona’s efforts to develop a vaccine against valley fever. Such dog-loving contributions over the past 20 years, along with support from a California pharmaceutical startup, have spurred researchers at the university. They say a canine valley fever vaccine could be available within the next 10 years, and work to save dogs from the disease could also advance efforts to create a vaccine viable for humans.
“I really think a dog vaccine is a realistic goal unless we have a scientific problem in the lab work that we didn’t anticipate,” said Dr Lisa Shubitz, veterinarian and associate research professor. at the AU School of Animal and Comparative. Biomedical Sciences, and part of the team working on the vaccine. “We believe that the dog is the way to the human.”
The live vaccine, a mutant spore invented by UA fungal geneticist Marc Orbach, is called delta-CPS1. He has already protected the mice from valley fever. Proving that it works in dogs is the next step.
Orbach invented delta-CPS1 after reviewing the work of a Cornell University researcher. This researcher, who studies a fungus that causes disease in corn, had identified a gene that this fungus needed to be pathogenic.
Orbach found a very similar gene in the coccidioides posadasii strain of the valley fever fungus. By splicing the gene, he created a strain of mutant spores that does not make animals sick.
Using this mutant strain, the Orbach laboratory was able to create a live attenuated vaccine. The risk of using a live vaccine is that the recipient – human or animal – will get sick with the disease the vaccine is trying to prevent. It was a concern for researchers. The safety data so far is impressive, but it has only been tested on mice.
The AU owns the intellectual property of the vaccine.
In 20 years, a total of $ 400,000 for the University of Arizona canine vaccine has been raised, all from dog lovers like Sit! Stay! Play! owner Janet Galante who has seen the heartbreaking toll disease can take on dogs.
“A lot of my clients’ dogs have valley fever. The emotional and economic costs are enormous,” said Galante.
“What they’re doing there is remarkable,” she said of the AU researchers. “If they’re doing this for valley fever, they’re going to open the door for other fungal diseases. It’s really important research.”
Donations often run as high as $ 20 or $ 30, from concerned and grieving pet owners. Larger donations have come from dog clubs and dog-related business owners.
“These add up, and I am infinitely grateful for the support, big and small, of those who have given to this project over the years, giving hope that we could accomplish this,” said Shubitz.
Part of the reason a dog vaccine is likely to hit the market sooner than a human vaccine is due to the different regulatory pathways it would follow. Vaccines for animals go through the Center for Veterinary Biologics of the United States Department of Agriculture (USDA) to be marketed, while a human vaccine would have to go through the Food and Drug Administration (FDA) of United States for approval.
“The regulatory process is very similar to humans, but it’s much more condensed for animals,” said Kwansun Ahn, CEO of Anivive Lifesciences, an Irvine-based veterinary pharmaceutical startup.
The AU has made progress in moving delta-CPS1 beyond the development stage by partnering with Anivive Lifesciences.
There is no sure-fire way to prevent valley fever, and once a person is infected, there is no cure. The disease, also known as coccidioidomycosis, sickens about 50,000 people a year nationwide, including about 30,000 Arizonans. Twice as many dogs as Arizona residents – about 60,000 – get sick with valley fever each year, Shubitz estimates.
Researchers are aware of past attempts to create a vaccine for humans. At least two previous attempts to create a valley fever vaccine have failed.
The first resulted in pain in the arms, but no conclusive evidence that it worked. The second attempt, a laboratory-created hybrid protein vaccine, looked promising, but failed due to cost.
Politics and funding are issues in bringing a valley fever vaccine to market, as the disease is concentrated in one region, the southwest. And because it affects less than 200,000 people per year, it is considered an orphan disease.
Unlike efforts to develop a human vaccine, the current dog vaccination effort begins with an actual spore. This eliminates the need for the costly protein purification step that has hampered recent attempts at human vaccines.
“I think this has a lot of promise and potential,” said Dr George R. Thompson, a valley fever expert and associate professor of medicine in the division of infectious diseases at the University of California at Davis. .
Delta-CPS1 researchers are optimistic about the grant applications they submitted to continue vaccine development – $ 6 million over five years from the National Institutes of Health (NIH) and $ 250,000 from Arizona Biomedical Research Commission. They expect to hear from both this year.
The AU team was encouraged to see that the NIH grant request for proposals specifically encouraged vaccines with low market potential and cited valley fever as an example, as well as Lyme disease and the virus. Zika. Federal officials say they expect to make funding decisions no earlier than late spring.
University of Arizona Valley Fever Center of Excellence director Dr John Galgiani believes the explicit mention of valley fever reflects what he sees as a keen interest in fever. from the House Majority Leader, Kevin McCarthy, R-Bakersfield, who is co-chairing a congressional task on valley fever. force with U.S. Representative David Schweikert, a Republican from Phoenix.
McCarthy and Schweikert have worked together to improve awareness and research on valley fever since 2013, when McCarthy hosted a symposium on the disease in Bakersfield, spurred in part by the Center for Health Journalism’s year-long reporting project. Collaborative on valley fever.
If the researchers don’t get the money, that doesn’t mean the canine vaccine won’t progress, but it will be a hurdle to overcome, Galgiani said.
The AU research team does not have an exact estimate of the cost of bringing a delta-CPS1 vaccine to market.
“We don’t have enough money to develop the vaccine, but the grant will take it forward,” Galgiani said. “I don’t think it’s going to be $ 40 million to get into the dogs. It could be in the range of $ 20 million, maybe as low as $ 10 million.”
TESTS TO INCLUDE LOCAL DOGS
Anivive officials have said they aim to market a canine vaccine in three to five years, although others say it could take up to seven years.
The vaccine has not yet been injected into dogs. The research team, which includes Orbach, Shubitz, and Galgiani, says it was advised to get more regulatory information from the U.S. Food and Drug Administration before beginning introductory safety studies. and immunology in dogs.
“We don’t want to undermine our position to authorize the vaccine by being premature,” Shubitz said.
Still, a delay of three to five years is possible, wrote USDA spokeswoman Donna L. Karlsons in an email.
Shubitz predicts that clinical trials of the vaccine will include dogs from Arizona and highly endemic areas of California, particularly the central valley around Bakersfield.
Shubitz said she has never been as optimistic as she is now. But she knows there is still a lot of work to be done.
“The reality is we have to capture this moment in time,” Shubitz said. “No one is going to pay for this twice. We have to be right.”
Some dogs with valley fever end up being euthanized because their owners cannot afford to treat them.
The antifungal drugs that are often needed to keep valley fever away for the rest of their pet’s life cost $ 4 to $ 6 per day, and the associated blood tests and vet costs can run into the thousands. Additionally, blood tests can give false negatives and require additional testing and money.
Dogs will often lose large amounts of weight and if the infection spreads to the bones it will affect their ability to move around. That’s what happened with Tyler.
“A vaccine would definitely save a lot of people a lot of heartache,” said dog owner Randy Ford, an aircraft mechanic. “Tyler was gorgeous. Mushroom is a bad thing.”
A 2005 study conducted by the AU found that dogs in Pima and Maricopa counties had a 28% chance of becoming infected with valley fever in the first two years of their lives. During this time, the risk of a dog getting sick was 6%.
The risk of infection was nearly five times higher for dogs who spent more than 80% of their time outdoors compared to dogs mainly indoors, according to the study. Dogs with more than an acre of land to roam were found to have a 6.2 times higher risk of infection than dogs with a smaller roaming area.
Company officials would not disclose the price of the vaccine, but said the intention was to create an affordable vaccine.
Shubitz said that even though the vaccine costs $ 100 per animal, it would be a steal compared to what many people are spending to treat the disease in their dogs, not to mention the emotional toll of seeing your pet become seriously ill. It is still not known whether the vaccine would work with a single dose or need to be given multiple times.