Fellowship Story Showcase
Valley Fever Vaccine Stalls
After years of promising developments, the effort to produce a valley fever vaccine is all but terminated because of a lack of funding and industry interest. Yet some still hope to see a vaccine on the market. This story is part of the ReportingonHealth Collaborative's "Just One Breath" investigative series on valley fever in California's Central Valley.
Just 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 they had selected a pathway to pursue a vaccine.
“A vaccine is at hand,” Dr. Richard Hector, the director of the umbrella organization, the Valley Fever Vaccine Project of the Americas, 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, including, most recently, the successful development of a vaccine to prevent the virus that causes cervical cancer. 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 U.S. Centers for Disease Control and Prevention’s chief expert in fungal diseases, adding that progress has been harmed by “neglect” and underinvestment.
EARLY VACCINE EFFORT FALTERED
Scientists for more than half a century have grappled with efforts 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 successfully 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 while people who visit the area or move there are hit harder.
When one vaccine was evaluated in the late 1970s and early 1980s, and 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 very sore arms and swelling at the injection site even at low doses. The shot was so painful people dropped out of the trials.
Ultimately, that vaccine didn’t show conclusive protection, something some researchers attributed to the low doses. For a vaccine potent enough to provide true immunization, people would have suffered too much pain to make vaccination practical, said Hector, now a researcher at the University of California, San Francisco.
The vaccine had reached the Phase III trial — human testing — which was as far as it could go, Hector said. The trial failed, and scientists had to start from scratch looking for different vaccines.
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. “Did it keep them from getting the (very serious) disseminated form? We don’t know.”
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 new vaccine with funding from the California HealthCare Foundation and the state of California.
The ambitious project was launched 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 following decade, an additional $5 million came from the California HealthCare Foundation. The federal government, the state, the county of Kern and nonprofit groups kicked in more, too. Total funding reached about $16 million.
But progress has faltered on this promising research enterprise because of the exorbitant costs of manufacturing and testing the experimental vaccine in today’s much more rigorously controlled research environment. The early vaccine of the 1970s, in contrast, made it to human trials much more cheaply and easily at a time when 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 laboratory conditions and advanced technology that greatly add to the costs, he said.
If funding was there, Galgiani said, he would be able to take his vaccine to human testing. For now, though, with scarce resources, he has been forced to shift his focus 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 CEO of the California HealthCare Foundation, said the foundation 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 email. “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 start of the recession in 2008 also took a toll on funding, and the state has had little discretionary money during the ensuing budget crisis.
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 and Kern County remain financially committed.
“We are still continuing to have different fundraising events and we’re conducting health fairs and different things to try to keep the grassroots going,” Cooper said.
The foundation has been able to invest close to $1 million over the years for the Valley Fever Vaccine Project, he said, but he admits that’s just a fraction of what the project needs. Some of the biggest donations to the foundation have come from the oil and natural gas industry. Aera Energy donated $100,000 in 2005 and Chevron Products Co. donated $30,000 that same year, said Bob Parker, the foundation’s treasurer.
Kern County has committed $50,000 for the current fiscal year.
DRUG COMPANIES IGNORE VALLEY FEVER
The amount of money raised to date is not enough to move a vaccine forward quickly. For a vaccine to be brought to market would require, by some estimates, an additional $100 million in research funding. At the current rate, it would take more than 60 years to raise that much money.
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, pancreatic cancer and a host of other conditions, including allergies to peanuts and cat hair.
But no U.S. pharmaceutical company currently is funding the development of a vaccine for valley fever, according to a 2012 report compiled by the trade association Pharmaceutical Research and Manufacturers of America (PhRMA).
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 emails and others did not want to speak on the record.
Merck spokesman Robert Consalvo said it can take more than a decade to develop a viable vaccine. Simply 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 now is encouraged to get a flu shot, and they are offered in drug stores and grocery stores nationwide.
Valley fever, so far, does not have the promise of a larger market on the horizon.
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 actually contract the disease every year, with most of them never being properly diagnosed. In those states where valley fever is prevalent, the rates of the disease are higher than those of many other common illnesses, including chickenpox and AIDS.
But, with the vast majority of cases concentrated in California and Arizona, most of the country doesn’t have to worry about the disease.
And the lack of a well-organized, disciplined patient lobby, such as the ones around HIV or breast cancer, doesn’t help the cause. Such patient groups always benefit from having a high-profile champion, and in this case, the most obvious candidates for celebrity spokespeople — baseball players who train in Arizona — aren’t speaking up, perhaps because speculation about their health could harm their baseball careers.
VACCINE RESEARCH LIMPS ALONG
The five scientists who were part of the high-profile vaccine research effort from 1997 are nearing retirement. One has died and another one is no longer doing valley fever research. Hector, who oversaw the work being done by the five scientists, lost his job when funding at the University of California, San Francisco ran out earlier this year.
The work of all five scientists reached the stage where they evaluated vaccines in mice, Hector said. One of them, Galgiani at the University of Arizona, also evaluated his vaccine in monkeys.
Three out of the five original scientists still are pursuing the development of a valley fever vaccine with small sources of funding, including some from the National Institutes of Health: Galgiani, Dr. Garry Cole, who worked at the Medical College of Ohio in Toledo and is now at the University of Texas at San Antonio, and Dr. Demosthenes Pappagianis at the University of California, Davis.
“All of the efforts are promising,” Hector said.
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.
We already use live viruses to immunize humans — including vaccines for measles and rotavirus — 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.
Photo credit: Dr. Demosthenes Pappagianis in the lab with his research staff inside Tupper Hall at University of California, Davis. By Brian Baer/Special To The Sacramento Bee