Dr. Lisa Shubitz and Marc Orbach did not set out to make a vaccine, let alone the world's first such vaccine. 

But this is exactly what they did, thanks to Auerbach’s connection with a corn geneticist, Schubitz’s lifelong passion for animals, new methods of vaccine manufacturing, and fundraising by a determined pet lover cadre effort.

Now, their team at the University of Arizona Valley Fever Center of Excellence announced that their new vaccine is very effective in protecting dogs from valley fever. The researchers said that this vaccine is the first vaccine against any kind of fungal disease, which is a milestone in vaccine research and genetics. 

This is also the most promising development in the long-term effort to prevent mysterious and sometimes debilitating infections. The fungus that causes valley fever lives in the soil of California and parts of the southwest, including large areas of Arizona. It affects humans and dogs. Although it does not cause symptoms in everyone, it can cause respiratory symptoms, joint pain, and sometimes even more serious complications that lead to serious illness or death.

The discovery of the vaccine not only relieved the dog owners, but also showed the hope of developing a human vaccine. The researchers said that now this seems to be within reach. 

"In general, the research we do is ultimately beneficial to humans and animals," said Schubitz, a veterinarian and research scientist at the University of Arizona. "The idea of ​​your commitment to helping people improve their lives is very beneficial."

Although many scientists are actively searching for useful drugs or products, Auerbach describes vaccines as the exciting end result of a scientific process driven mainly by open curiosity.

Auerbach, a professor of plant pathology and microbiology at the University of Arizona, said: “When we conduct basic research, we always have a goal, that is, our research will bring important results in response to disease.” “It’s really effective, it’s beyond Our craziest dream."

Auerbach was initially not curious about humans, dogs or even mice. He was inspired by a friend's research on corn, or more specifically, a fungus that attacks it.

Auerbach’s friend Gillian Turgeon, a Cornell University researcher, is telling him about her research on diseases that affect corn. Her team discovered that they can change specific genes in corn-targeted fungi to reduce its damage to plants. Auerbach wanted to know if he could change genes in other types of fungi, such as the coccidioidomycete that causes valley fever.

"There are fungi that specifically infect plants and fungi that specifically infect animals, but some genes are conserved between (the two)," Auerbach said. "This is (this) gene is an example."

So Auerbach and his team set out to adjust the fungus's DNA. When they deleted the gene of interest cps-1, they realized that mice infected with the mutant fungus would not get sick.

They knew they created a valley fever of disarming. But they are not sure whether it will actually produce immunity.

For decades, the prospect of developing vaccines against fungal diseases has been daunting. This is because the immune response responsible for neutralizing Valley Fever is completely different from the response to other diseases. 

When naturally infected with Valley Fever, the body will eventually find a way to control the fungus without actually getting rid of it. This is similar to what happens with the virus that causes chickenpox. But unlike most viruses-SARS-CoV-2, for example, which is covered with many of the same "spike" proteins-fungi have many types of proteins that the host can recognize. Researchers are not sure which of these proteins actually participate in the immune response.

But because Auerbach’s harmless version of Valley Fever is exactly the same as ordinary Valley Fever, except that it has no disease-causing part, it has all these proteins built in. This means that they can induce a response similar to a natural infection without having to hone the University of Arizona Professor of Medicine and Director of the Valley Fever Center of Excellence Dr. John Galgiani explained that a single protein is technically difficult and more expensive to manufacture.

"(The body) will not kill (the fungus that causes valley fever). It will only put it into sleep," Galgiani said. "And we don't quite understand what'sleep' is. This is a very interesting question." 

However, Galgiani said that a live vaccine like this is often one of the "best vaccines in the world." So they decided to test it on mice to see if it worked.

It did. Mice that had previously received a mutant, harmless strain of Valley Fever did not become sick when exposed to the virus-causing strain. "The results are so compelling," Galgioni said. "The vaccine looks very good, (even) in the first experiment... the more we study, the better it looks."

In 1998, Schubitz’s dog, a whippet named Arrow, was diagnosed with valley fever. The medication to treat her costs $10 a day, and even after three months, Arrow still has a fever and signs of lung disease. 

In the end, they found another helpful drug, but Schubitz said that this was her personal experience of caring for dogs with valley fever, which inspired her to continue the trials needed to make a canine vaccine. "(Arrow) let me enter (to study Canine Valley Fever)...before I was just a mouse," Schubitz said.

But Schubitz's interest is not enough; her laboratory needs funding. This is where the wider community intervenes.

"This is the vaccine that dog owners really use... They have been donating money for many years," Schubitz said. "Working with dog owners is really humble. These people are very concerned about the disease in Arizona." 

Galgiani estimated that the total amount of charity for dog owners was approximately $200,000. These funds provided funding for preliminary research, which eventually received grants from NIH and additional funding from Anivive Lifesciences, an animal pharmaceutical company based in Long Beach, California.

The dog experiment paid off. All the vaccinated dogs in the study either showed no signs of disease or the symptoms were so mild that they were clinically irrelevant.

Now, these results will pave the way for vaccines actually used by dog ​​owners. Auerbach said: "We think it is realistic that there will be a commercial vaccine for dogs in the next year or so."

Shubitz attributes the success of the new vaccine to a bit of luck and a lot of teamwork. "A lot of science is discovered by accident, and then hard work," she said. "(Science) is not a job done by one person. It is done by many people, and they bring a variety of expertise."

Galgiani said that he is not only excited about the genetic technology that led to the discovery of the vaccine, but also excited about the feasibility of creating an economically viable final product.

"This is the spore in the bottle... We just grow the spore, and this is the vaccine," Galgiani said.

Dr. David Bruyette, Chief Medical Officer of Anivive Lifesciences, explained that this process is revolutionary in its own way. Bruyette said that in general, fungus is the last thing vaccine manufacturers want in their facilities because it is considered a contaminant of viral or bacterial vaccines. Therefore, they must create a new method for mass production and packaging of harmless coccidioides spores.

After putting the correct number of spores into the vial, the manufacturer will deep freeze the vial through a special process to preserve the fungus without water. This will turn them into a powdered substance, which the veterinarian can then use a saline solution to turn them into an injectable form. 

"What you see in the vial... is like foam, it looks like marshmallows," Bruyett said. 

He added that this new technology is not only expected to eventually develop a human vaccine against valley fever, but also can be extended to develop other vaccines against diseases that affect pets across the country.

"There are three endemic fungi in the United States," Bruyett said, adding that these species can cause pets to get sick. "Then Cryptococcus (Cryptococcus neoformans), (this is) a devastating disease worldwide."

Galgiani said that due to complex genetic factors, people of color may be more susceptible to Valley Fever than people of European descent. Bruyette also pointed out that fungal diseases tend to make vulnerable people the most serious because people with weakened immune systems are least able to neutralize the disease. Popular fungus. 

"I think we see that the U.S. government is very interested in funding more research on these diseases, and of course (in) looking for ideas to create these different fungal strains that will not make you sick, but can stimulate your immune system. Said Bruyett.

In October 2019, Dena Olsen had a cough that would not go away. She found it difficult to speak without coughing, and it was even difficult to fall asleep. Her doctor tried various treatments, but none seemed to be effective.

Then she took her dog for an annual check-up, and her family veterinarian heard her cough. The vet told her that she needed Valley Fever treatment.

Olsen proposed this idea to her doctor, and after four weeks of taking the valley fever medicine, Olsen's cough disappeared. Olsen thinks her vet cured her after months of exhaustion.

"Whether it is an animal or a human, you have the same symptoms," Olsen said. "It's very stressful for me and my family."

Even so, Olsen said, if someone provided her with a valley fever vaccine, she would not get it. "I don't like putting foreign objects in my body to prevent certain things from happening," she said.

Jennifer Schaefer's family experienced strains similar to Olsen, but Schaefer said that one day she will become the first human vaccine against Valley Fever. Her mother was diagnosed with Valley Fever 20 years ago and stayed in the hospital for a week after contracting pneumonia. Even now, she can still feel the lingering effects, including what Schaefer calls a "violent cough."

Last fall, Schaefer's English Mastiff also contracted Valley Fever. They took Piper to the veterinary neurological center to treat epilepsy. At the worst, they had to take more than 20 pills a day.

"This is a long and difficult road," Shafer said. "(Dog) can't tell you how they feel."

She described the lack of preventive care for Valley Fever as heartbreaking and expressed excitement about the prospect of an upcoming canine vaccine. 

"Having this vaccine is incredible," she said. "It can keep many animals alive."

Independent reporting on the biological sciences of Arizona was funded by the Flynn Foundation.

Melina Walling is a bioscience reporter covering COVID-19, health, technology, agriculture and the environment. You can contact her via email mwalling@gannett.com or Twitter @MelinaWalling.