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Saturday, May 18, 2024

A Vaccine Against Valley Fever Finally Works—for Dogs

An experimental vaccine that could protect millions of people living in the American Southwest from valley fever—an infection caused by a soil-dwelling fungus that is difficult to treat and can cause disability and death—has passed its first test of efficacy and is moving toward federal approval, possibly within two years.

The catch: The vaccine was tested in, and will be developed for, dogs. A formula that could be given to humans, if it can be achieved, lies many years and millions of dollars down the road. But researchers say even this first step is notable, a significant milestone on the way to preventing potentially hundreds of thousands of human cases a year.

To be clear, this vaccine is needed for dogs, too. They aren’t just a model system for lab work; for reasons that are not well understood, they develop the disease and its most severe manifestations at higher rates than humans do. Possibly 30 million dogs live in the area endemic for valley fever, which centers on Arizona, stretches from California to West Texas, and reaches into Nevada and Utah. In some Arizona counties, 1 in 10 dogs develops the disease each year, and it is the No. 1 cause of dogs being surrendered to animal control. A vaccine that could protect them would save loved pets from suffering and reduce the costs borne by owners and shelters.

The vaccine candidate, which was developed by the Valley Fever Center for Excellence at the University of Arizona College of Medicine, uses a version of one of the fungi responsible for the infection, from which a gene that controls virulence has been deleted. Working with researchers at other universities and biotech startup Anivive Lifesciences of Long Beach, California, the team inoculated dogs with a solution containing live spores from the altered fungus. They found a two-dose regimen of an initial shot and a booster was safe and protected dogs against developing disease when they were exposed to wild fungus in the lab. The results were published ahead of October inclusion in the journal Vaccine.

“We think the results are very convincing that the vaccine shows robust protection in this model—and it’s an aggressive model, compared to wild-type infection,” says John Galgiani, senior author on the paper and director of the University of Arizona center. The group is working now on scaling up the small-batch prototype developed in his lab to produce a shelf-stable formula that could be commercialized for use in dogs. The team will then submit it to the US Department of Agriculture, which regulates animal vaccines, for conditional approval. They hope to see it distributed by 2023.

It’s the first good news in a long trail of disappointments that stretches back to the 1980s, when Galgiani was part of a thinly funded research group investigating a human vaccine candidate based on inactivated fungus. The trial was unsuccessful—the injection-site reactions were too painful—and from then on, there has been no vaccine for valley fever, nor for any fungal disease.

In addition to submitting the formula’s portfolio to the USDA, the next step is to run a safety trial with about 600 dogs in the real world. Owners would volunteer their pets to receive the vaccine for free in exchange for having their dogs examined a month later, says Dylan Balsz, Aninive’s founder and CEO. Once the vaccine is licensed, the goal would be to sell it to veterinarians, providing a preventive alternative to the year-long, and sometimes lifelong, courses of drugs that dogs must be given once they are infected.

With luck, the income from those sales—Balsz estimates the price might range from $30 to $60 per dose—could bootstrap the rest of the company’s portfolio, which includes rights to develop the candidate as a human vaccine. For that effort, they would seek additional partners. Anivive’s core business is mining the research literature for abandoned compounds that can be repurposed as veterinary medications. “But this has been our obsession,” Balsz says. “I didn’t appreciate that there has never been a fungal vaccine.”

A human formula is what fungal-infection experts most hope to see. “We definitely need a vaccine,” says George Thompson, an associate professor of medicine and codirector of the Center for Valley Fever at the University of California, Davis, which is both a major treatment center for human patients and the institution where that first unsuccessful vaccine was tested. “This is a disease that continues to increase yearly, and it affects our most vulnerable populations: farm workers, solar-field construction workers in the Central Valley. Those are groups that don't have resources for health care if they experience the complications of valley fever. So preventing it through a vaccine would really be a huge leap forward.”

Several things have made it difficult to counter the threat of valley fever—technically coccidioidomycosis, caused by the organisms Coccidioides immitis and Coccidioides posadasii. First, it is caused by a fungus. That means it is more like us, on a cellular level, than bacteria or viruses are. Drugs that can kill fungi may also damage our cells.

But also, while fungal infections are a massive problem worldwide—one organization estimates there may be 300 million people infected and 1.6 million deaths every year—valley fever is a niche disease within that group. Its range seems to be confined to the western US, Mexico, Central America, eastern Brazil, and northern Argentina. The latest count of US confirmed cases was 18,407 in 2019, though researchers estimate the true count could be 150,000 cases or higher.

The delta between known and suspected cases is due to a complex set of factors. Not everyone who breathes in the spores, which break free from the fungus in the soil in dry times and can travel hundreds of miles, develops illness. Those who do may mistake its symptoms of fever, cough, and fatigue for the flu. Only about 10 percent of infected people develop serious manifestations, such as fungal growths that occlude their lungs, and only about 1 percent develop the most dire complications: fungal invasion of their bones, joints, spine, and brain.

Plus, because valley fever is a regional disease, a physician needs regional knowledge to recognize its existence. Someone working in New York City might not consider it the way a physician in Las Vegas would. Compounding that lack of recognition, only 26 states (plus Washington, DC) rank it as something public health authorities have to be notified about. And although California is one of the most-affected states, second only to Arizona, California’s affluent tech workers rarely develop the disease. Its chief victims are people who are already immunocompromised or who work outside or are exposed to warm, windy, dusty conditions: not only farmworkers, but contractors, road crews, and excavators and homebuilders laying out subdivisions.

Others at risk: military personnel assigned to southwestern bases and winter vacationers from cold northern states, all of whom return home to places where doctors are unlikely to recognize the illness. As I wrote for Scientific American this summer, in 2018, CDC epidemiologists doing a nationwide sweep for the disease found cases in 14 states that mostly lie along the Canadian border—places so cold that the infections could not have occurred there. After unravelling the patients’ past travel, investigators recognized the individuals had been infected somewhere to the south and brought the fungus home.

“If we achieved a vaccine, definitely people who lived in the endemic area would be where to start, people who are immunocompromised,” Thompson says. “But it also might become a mainstay of travel medicine. A travel advisory before visiting certain locations would be interesting to contemplate—though I don’t envision states wanting to caution people to get vaccinations before visiting.”

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The WIRED Guide to Climate Change

The world is getting warmer, the weather is getting worse. Here's everything you need to know about what humans can do to stop wrecking the planet.

By Katie M. Palmer and Matt Simon

Valley fever is estimated to cost the US $3.9 billion per year, and by one estimate, a vaccine could save potentially $1.5 billion in health care costs every year. But that cost, and thus the urgency to achieve a vaccine, is almost certain to increase because climate change is expanding the locations where valley fever is an infection risk. The fungus responds to temperature and humidity: It needs a warm environment to thrive, and in damp conditions it remains quiescently in the soil. But as climate warming increases, new territory will open up for Coccidioides, and shifting rainfall patterns mean areas where it has begun to grow will dry out enough for it to break apart and drift. There is already a known area of vulnerability in the center of Washington State, a place that was previously thought to be too cold for the fungus. In 2010, three people contracted valley fever there, including a construction worker and a teen who had been roaring around on an ATV.

In 2019, Morgan Gorris, an Earth system scientist at Los Alamos National Laboratory, used temperature and rainfall data to estimate more precisely where valley fever is endemic, based on the fungus’s known behavior in ranges of humidity and warmth. Using those findings, and combining them with different climate-warming forecasts, she modeled how valley fever’s range might expand under different scenarios of greenhouse gas emissions. Under the highest-warming scenario (a global rise of almost 9 degrees Fahrenheit), the area where the disease could become endemic would double in size by the year 2100, covering 17 states, including Idaho, Wyoming, Montana, Nebraska, and the Dakotas. The number of cases, the model predicted, would rise by half. In another analysis based on that work, she estimated that by the year 2100, the cost of valley fever to the US would reach $18.5 billion per year.

That looming bill, along with the illness and death underlying it, may be the best rationale for reaching to develop a vaccine. “Climate change is going to exacerbate ongoing threats and cause new threats,” Gorris says. “We’ll need resources in the future to adequately combat emerging diseases. Having a vaccine to address the risk of valley fever will allow us to free up resources to tackle other climate change issues, especially those related to human health.”

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