Valley fever vaccine a hostage to cash

Reporting on Health CollaborativeOctober 6, 2012 

— Eight years ago, a vaccine to stop valley fever seemed within reach.

Ambitious scientists at five universities had brought in millions of dollars since 1997 from private donations and government funding to develop a way to beat the fungus before it ever had a chance to lodge in a person's lungs and wreak havoc on his or her organs.

In 2004, they announced selection of a path to pursue a vaccine.

"A vaccine is at hand," Dr. Richard Hector, director of the Valley Fever Vaccine Project of the Americas, an umbrella organization, told an excited group of scientists at California State University, Bakersfield.

But today, early animal trials of experimental vaccines have ground to a halt. Research funds have dried up. And the once thriving academic effort has slowed dramatically.

Private industry interest is critical to bringing a vaccine out of the laboratory and into doctor's offices and clinics. That has been the pattern for all modern vaccines. But there has been no interest by big pharmaceutical companies in investing in valley fever.

"Certainly, we think that more attention is needed on finding new effective treatments as well as preventive measures, like a vaccine," said Dr. Benjamin Park, the Centers for Disease Control and Prevention's chief expert in fungal diseases. Progress has been harmed by "neglect" and underinvestment, he added.

Early effort faltered

For more than 50 years scientists have grappled to develop a valley fever vaccine. The disease is tricky. The fungus that causes it infects a person for life and can never be removed from the body. But if a person fights off the disease, he or she is immune to future infections. That's why people who grew up in areas where the fungus is prevalent often avoid serious illness, but people who visit the area or move there are hit harder.

One vaccine evaluated in the late 1970s and early 1980s proved to be effective in mice and monkeys. Hundreds of people signed up for the human clinical trials.

But there was a problem.

Patients complained of sore arms and swelling at the injection site even at low doses. The shot was so painful people dropped out of the trials.

That vaccine didn't show conclusive protection, which some researchers attributed to the low doses. For a vaccine potent enough to provide immunization, people would have suffered too much pain to make vaccination practical, said Hector, now a researcher at the University of California at San Francisco.

The vaccine had reached the Phase III trial -- human testing, Hector said. The trial failed, so scientists had to start from scratch looking for a vaccine.

That unsuccessful trial also left a lot of questions unanswered, said Dr. Thomas Larwood, a retired Bakersfield physician who worked on the project.

"It didn't keep people from getting cocci," Larwood said, using the abbreviation for coccidioidomycosis. "Did it keep them from getting the (very serious) disseminated form? We don't know."

Optimism in the air

For more than a decade after those tests, vaccine research languished. Then, in 1997, a Bakersfield-based committee worked with California State University, Bakersfield to select five U.S. scientists to develop a vaccine with funding from the California HealthCare Foundation and the state of California.

The ambitious project started with a $1.5 million grant from the foundation, a $700,000 state fund, sponsored by Assemblyman Roy Ashburn, R-Bakersfield, and a contribution of more than $100,000 from the Rotary Club.

Over the next decade, $5 million more came from the foundation. The federal government, the state, Kern County and nonprofits kicked in more, too. Total funding reached about $16 million.

But progress has faltered because of the exorbitant costs of manufacturing and testing the experimental vaccine in today's more rigorously controlled research environment. The early vaccine of the 1970s made it to human trials much more cheaply and easily because there were fewer quality control requirements and regulatory hurdles, Hector said.

Today, scientists are working on more sophisticated approaches that are more expensive and challenging to make.

For example, Dr. John Galgiani, a professor of medicine at the University of Arizona and the director of the Valley Fever Center for Excellence, has been working on a vaccine built from a specific protein. The work requires pristine lab conditions and advanced technology that greatly add to the costs, he said.

If funding were there, Galgiani said, he would be able to take his vaccine to human testing. But with scarce resources, he has been forced to look for ways to make the vaccine cheaper to manufacture.

Nearly all the money raised during the early excitement for a new vaccine has been spent and donations have dwindled, said Michael Cooper, president of the Valley Fever Americas Foundation, which raises funds for the vaccine project.

Dr. Mark D. Smith, president and chief executive officer of the California HealthCare Foundation, said it stopped supporting the vaccine project because the foundation is not set up to thoroughly evaluate such scientific research.

"Basic science is extremely expensive," Smith wrote in an e-mail. "The researchers we funded had encountered a number of technical and scientific obstacles (not uncommon in vaccine development). We simply weren't in a position to evaluate the merits of alternative research strategies, particularly at that price."

The recession and the state's budget crisis have had an effect as well.

However, in the wake of the Reporting on Health Collaborative's series on valley fever, state Sen. Michael Rubio, D-Shafter, said he intends to try to revive state funding for vaccine research.

The Valley Fever Americas Foundation remains financially committed.

"We are still continuing to have different fund-raising events and we're conducting health fairs and different things to try to keep the grass-roots going," Cooper said.

The foundation has invested close to $1 million over the years for the Valley Fever Vaccine Project, he said.

Kern County has committed $50,000 for the current fiscal year.

Ignoring valley fever

For a vaccine to be brought to market would require, by some estimates, an additional $100 million in research funding. Galgiani estimated it would take $40 million just to begin human clinical trials.

That's the kind of money only the pharmaceutical industry can provide.

U.S. pharmaceutical companies are working on about 300 vaccines for diseases, including HIV and pancreatic cancer. But no U.S. pharmaceutical company is funding development of a vaccine for valley fever, according to a 2012 report compiled by the trade association Pharmaceutical Research and Manufacturers of America.

The Reporting on Health Collaborative contacted nine U.S. pharmaceutical companies to ask what might be holding back interest in funding valley fever research. Most companies didn't return telephone calls and e-mails and others did not want to speak on the record.

Merck spokesman Robert Consular said it can take more than a decade to develop a viable vaccine. Fronting the cost and managing the logistics of enrolling hundreds, if not thousands, of patients for human studies can be a significant undertaking, Consalvo said.

To pay for that kind of investment, drug companies often look for vaccines that will have a market that will expand over time. The annual influenza vaccine, for instance, was initially marketed to parents with young children, older adults and people with compromised immune systems. But the market has grown to the point where everyone is encouraged to get a flu shot.

Valley fever does not hold out such promise. The Centers for Disease Control and Prevention found that more than 20,000 people officially came down with valley fever in 2011 nationwide, and multiple studies estimate that more than 150,000 people contract the disease every year, most of whom are never properly diagnosed.

In those states where valley fever is prevalent, the disease rate is higher than those of many other common illnesses, including chickenpox and AIDS. But the vast majority of cases is concentrated in California and Arizona.

Research limps along

Three of the five scientists from the 1997 research effort still are pursuing the development of a valley fever vaccine with small sources of funding: Galgiani, Dr. Garry Cole, University of Texas at San Antonio, and Dr. Demosthenes Pappagianis at the University of California at Davis.

Pappagianis said the live vaccine being studied by Cole's team is a "nice accomplishment."

"It was an important development to have such a live vaccine available to prove that it can be protective, but putting it to use could be problematic," Pappagianis said.

Live viruses to immunize humans, including vaccines for measles and rotavirus, are used. But there's still considerable reluctance to do so, Pappagianis said, because of the fear that the vaccine might infect people with the disease or cause a related infection.

For many years, people with polio were given a live vaccine and some of the recipients developed a severe infection.

Asked how long and how much money it would take to make his vaccine available to the public, Cole said: "That's the million-dollar question."

Kellie Schmitt from the Reporting on Health Collaborative contributed to this report.

Vaccine researchers

Five scientists were chosen by a committee affiliated with California State University, Bakersfield, in 1997 to pursue vaccine research.

DR. JOHN GALGIANI, 66, professor at the University of Arizona and director of the Valley Fever Center for Excellence

Developed a vaccine that has been tested in mice and monkeys

Currently working to improve the vaccine to make it cheaper to make

Working on Nikkomycin Z, a potential valley fever cure

DR. DEMOSTHENES PAPPAGIANIS, 84, professor and director of the Coccidioidomycosis Serology Laboratory

at the University of California at Davis

Began studying the coccidioides fungus in the early 1950s

Currently conducting vaccine tests

on mice

Trying to find the right formulation

to generate a strong immune response

Studying how many doses of the vaccine have to be given, and precisely when, in order to get the maximum effect

DR. GARRY COLE, 71, professor and chairman in medical mycology at the University of Texas at San Antonio

Generated a live vaccine that has been tested in mice

Vaccine has been attenuated, meaning weakened, to make it safe for immunizations

Working to modify vaccine to confirm that, once injected, it would not become infectious

Hoping to test the vaccine in primates and, eventually, humans

Developing a second vaccine with a different formulation

DR. REBECCA COX, 62, scientist at the University of Texas Health Science Center at San Antonio

Studied the coccidioides fungus

for 30 years.

Focused on the role of the human immune system in combating the fungus once it is inhaled

Died July 14, 2006

DR. THEO KIRKLAND, 62, professor

of pathology and medicine at theUniversity of California at San Diego

Tested a vaccine in mice but wasn't able to pursue it further

Stopped doing research on valley fever after funding for his project ran out

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