28 August 2006

Pitt scientists get $1.3M grant for bird flu vaccine

Pitt scientists get $1.3M grant for bird flu vaccine
By Jennifer Bails
Friday, August 25, 2006

University of Pittsburgh researchers said Thursday they have received a $1.3 million federal grant to begin production of a promising new bird flu vaccine they hope will protect people from the deadly virus.
Pitt virologist Dr. Andrea Gambotto announced in January he had genetically engineered a vaccine that protected 100 percent of mice and chickens from illness and death caused by a strain of avian influenza that has decimated poultry flocks and killed dozens of people in Asia.

For the past seven months, Gambotto has been awaiting money from the National Institutes of Health to begin clinical trials to test the safety and effectiveness of the vaccine in humans.

Thanks to the two-year grant awarded Aug. 1 by the NIH, production of a master batch and several additional lots of clinical-grade vaccine for those trials is beginning, said Gambotto, co-director of Pitt's Vector Core Facility.

We will go into production three weeks from now, and then test the quality of the vaccine," he said. "We hope that by the end of the year, or at least by early next year, we will have a product to do the clinical study."
The vaccine will be created and rigorously tested in Pitt's Good Manufacturing Practices laboratory, a "clean" facility in Hazelwood that meets the federal criteria for making biological products that will be administered to people.

It must then be approved by the U.S. Food and Drug Administration before clinical trials could begin. Meanwhile, the Pitt researchers will decide how those trials should proceed.

"We will probably compare intramuscular injection of the vaccine to intranasal use, but we have to define the number of patients and dosage escalation," Gambotto said.

Bird flu infects birds, but does not spread easily among humans.

Since 1997, 241 known human cases of infection with a strain called H5N1 have occurred in Asia and Europe, killing 141, according to the World Health Organization.

Most of the victims had contact with dead or sick birds, or their blood or excrement.

But health officials are ramping up efforts to prepare for a global bird flu pandemic, fearing the virus could mutate into a form easily transmissible from person to person.

There is no commercially available vaccine for people.

Last month, pharmaceutical giant GlaxoSmithKline reported that low doses of its bird flu vaccine protected about 80 percent of 400 healthy people inoculated in Belgium.

Earlier this year, a vaccine manufactured by Sanofi Pasteur was shown to protect only about half of test subjects.

"They have not been very encouraging results," Gambotto said.

These vaccines were created by brewing a form of the H5N1 virus - stripped of the disease-causing gene - in fertilized chicken eggs.

The decades-old technology takes four to six months to complete. Another problem with these traditional killed-virus vaccines is they only protect against one viral strain - a major drawback since the bird flu virus appears to be evolving quickly.

Gambotto's first-of-its-kind vaccine is quick to make inside the controlled confines of a laboratory dish and could protect against many strains of avian influenza.

In a process that takes just a couple of weeks, he uses the genetic information from a particularly lethal strain of H5N1 to generate bits of key bird flu proteins.

Gambotto packs those protein fragments, called antigens, inside a relatively harmless cold virus that shuttles them into the body. The protein bits cannot cause disease, but are meant to prime the immune system to recognize and destroy the wild virus.

The vaccine triggered chickens and mice in Gambotto's animal studies to produce antibodies that attacked the invading virus. Unlike the other vaccines being tested, it also stimulated production of immune cells called T-cells that could give the vaccine power to target multiple strains of the ever-changing virus, he said.

"It would certainly be nice to have this vaccine should there be an outbreak of H5N1," leading bird flu expert Richard Webby, of St. Jude Children's Research Hospital in Memphis, Tenn., said when Gambotto reported his results.

Since that time, Gambotto has refined his vaccine by adding more antigens that could be used to stimulate the immune system to fight the bird flu, he said.

Gambotto is optimistic his vaccine could work, but he hopes the bird flu will never mutate into a pandemic form that makes its use necessary.

"Hopefully, our vaccine will only be a scientific exercise," he said. "This is the best vaccine."

Jennifer Bails can be reached at jbails@tribweb.com or (412) 320-7991.

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