S.D.'s Vical is working on novel approach: a DNA vaccine
By Penni Crabtree
UNION-TRIBUNE STAFF WRITER
November 11, 2005
DON KOHLBAUER / Union-Tribune
Denis Rusalov, a research associate at Vical, examined a formulation agent for purity. The San Diego company has received a $2.9 million grant from the National Institutes of Health toward development of a DNA vaccine against avian flu.
While the Bush administration's $7.1 billion plan to deal with the threat of an avian flu outbreak is largely focused on the production and stockpiling of traditional vaccines, the grim logistics of a potential pandemic provide an opportunity for drug companies with more novel approaches.
One of the biggest flu challenges facing world health leaders is time.
If a pandemic were to emerge in the next year, it would take months before full-scale global vaccine production could begin using conventional methods of making vaccines in eggs, according to some studies.
Even then, the world's flu vaccine plants can produce only about 450 million shots over six months – which would protect less than 10 percent of the world's population.
With that in mind, the U.S. government is funding research at some biotechnology companies, including San Diego's Vical, to explore new kinds of vaccines that might treat or prevent the H5N1 "bird flu," the most dangerous strain of influenza to appear in decades.
In September, Vical received a $2.9 million grant from the National Institutes of Health toward development of a DNA vaccine against avian flu.
Vical is collaborating in the effort with St. Jude Children's Research Hospital in Memphis, considered a center of expertise in influenza research.
The biotech also received a $500,000 grant from the U.S. Department of Defense to do feasibility studies of a new approach for rapidly manufacturing large quantities of DNA vaccines.
Vical's DNA vaccine is designed to target core virus proteins that are common across flu strains, then add to it the surface proteins specific to whatever form of avian flu that might emerge.
Once the gene sequence of a new virus strain is known, it can take as little as three months for initial production of a DNA vaccine. Vical is evaluating ways to reduce that time to weeks.
The goal is to develop an effective vaccine that can be made quickly and stockpiled longer than a traditional vaccine made from killed virus.
A DNA vaccine that contains the genetic code for a protein on the surface of the H5N1 virus would teach the body to recognize the invading virus, and mount an immune response in much the same way as a conventional virus.
The quest for more ways to tackle avian flu is gaining more urgency as the lethal virus makes its way from country to country.
More than 160 million birds have died or been destroyed in Asia as a result of the virus, and 65 people out of about 120 infected have died, according to the United Nations' World Health Organization.
So far, the H5N1 virus has not shown it can spread easily from person to person, but that could be just a genetic skip and mutation away, many agree.
Medical experts fear H5N1 because it is a member of a virus family that can cross species – in this case from birds to humans.
The avian flu has the ability to change its protein arrangements, either through mutation or mixing with human viruses, to create a new, highly infective form to which people have no natural immunity.
History has shown that a bird-to-human flu can be devastating. The 1918 Spanish Flu, which originated with birds, killed 40 million people worldwide, including about 500,000 in the U.S.
If the current strain of avian flu were to hop over to humans, an estimated 30 percent of the U.S. population would become sick, 9.9 million would be hospitalized, and as many as 1.9 million could die, according to estimates by the Department of Health and Human Services.
Under the Bush proposal, the government plans to spend about $1.5 billion to stockpile 20 million doses of an experimental vaccine based on the bird flu virus now circulating in Asia.
That vaccine, which has shown promise in NIH testing, is made by the Sanofi-Aventis Group of France.
An additional $1 billion is earmarked for stockpiling anti-viral drugs to reduce the flu's severity, $2.8 billion to develop news ways to manufacture vaccines, and about $800 million to develop new flu treatments.
Vical acknowledges that its potential DNA vaccine is no panacea. But it might prove to be a stopgap solution during a pandemic as the world tries to ramp up production of a conventional killed-virus vaccine.
Dr. David Kaslow, Vical's chief scientific officer, said a DNA vaccine would probably not prevent someone from contracting the avian flu. But it could significantly reduce its severity and buy time for the body to mount an immune response and produce antibodies to attack the virus.
"We think this would give people protection, not against the symptoms, but some protection until a perfect H5N1 vaccine is made," Kaslow said.
How well, or even if, Vical's vaccine will work remains a big question. The veteran biotech company has tested a variety of experimental DNA vaccines for tough diseases such as cancer, but has yet to come up with one that works.
But Vical has improved its DNA vaccine technology over the years, and the science recently scored a success with the back-to-back approval earlier this year of the world's first DNA vaccines – though in animals, not humans.
Swiss-based Novartis Animal Health, using technology licensed from Vical, received approval for a DNA vaccine to protect farm-raised fish from a deadly virus. Another DNA vaccine to protect horses from West Nile disease was also approved.
The NIH is now exploring Vical's technology to develop vaccines against other viruses, including HIV, SARS, Ebola and West Nile.
In various scientific meetings, NIH researchers have reported that DNA vaccines have generated an immune response in HIV and Ebola virus studies, but the data have not yet been published.
Dr. Gary Nabel, director of the NIH's Vaccine Research Center, said the immediate global need is to stockpile traditional vaccines and antibiotics, and speed production of both.
But there is also a need to "explore other platforms, ways that in two or three years we could be more effective in responding than we are today," he said.
"Clearly the pandemic flu threat has given us a wake-up call in terms of how we approach the problem," Nabel said. "DNA vaccine technology is not going to help us immediately, but it is a technology that needs to be explored and needs to find its place."
Penni Crabtree: (619) 293-1237; penni.crabtree@uniontrib.com
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