Bird Flu Alarm

2006-01-27-Bird flu breakthrough

Understanding Avian Influenza

2006-01-27-Bird flu breakthrough

University of Pittsburgh researchers have genetically engineered a vaccine that stops bird flu from killing mice and chickens -- and could better protect humans against a global outbreak of avian influenza than other experimental vaccines.

The new vaccine completely protected the animals from illness and death caused by a strain of the virus that has decimated poultry flocks and killed dozens of people in Asia, Dr. Andrea Gambotto, co-director of Pitt's Vector Core Facility, said Thursday.

"Bird flu may likely become the next pandemic, and this vaccine is worth investigating further," said Gambotto, who is seeking about $2 million from the National Institutes of Health to begin testing the safety of his vaccine in people.

Bird flu -- also called H5N1 -- infects birds, but does not spread easily among humans. Since 1997, about 170 known human cases of H5N1 infection have occurred in Asia and Europe, killing 83, 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 bird flu pandemic, fearing the virus could mutate into a form easily transmitted from person to person.

There is no commercially available vaccine for people, but if Gambotto's vaccine is approved for widespread use in poultry, and perhaps other birds, it could create a barrier to prevent the virus from spreading to humans.

In 2004, the NIH awarded two contracts for production and clinical testing of experimental human vaccines against H5N1 to pharmaceutical makers Sanofi Pasteur in Swiftwater, Monroe County, and Chiron Corp. in Emeryville, Calif. Results from these trials are expected this year.

Like seasonal flu vaccines, these bird flu vaccines were created by incubating a form of the H5N1 virus -- stripped of a disease-causing gene -- in fertilized chicken eggs. The decades-old technology takes four to six months to complete. Another problem with these so-called killed-virus vaccines is they only protect against one viral strain -- a major drawback given how quickly bird flu appears to be evolving.

Members of Gambotto's research team, however, used a faster method they say could potentially provide immunity against many strains of bird flu.

"I think it's a step in the right direction," said Dr. Nicole Baumgarth, a cellular immunologist at University of California, Davis, who wasn't involved in the research. "We need to do something different than the type of vaccines we currently have because it takes too long to make them."

In February 2004, Gambotto acquired the genetic code of the particularly lethal Vietnam strain of H5N1 from scientists at the U.S. Centers for Disease Control and Prevention.

Thirty-six days later, his team had constructed its vaccine by using this genetic information to generate bits of a key bird flu protein.

The Pitt scientists then packaged these protein fragments inside a relatively harmless cold virus. The cold virus shuttles the proteins into the body. The proteins cannot cause disease, but they prime the immune system to recognize and attack the wild pandemic virus.

With the help of researchers at the CDC and the U.S. Department of Agriculture, Gambotto and his colleagues tested the ability of their vaccine to protect mice and chickens from infection. Mice injected with the vaccine all survived when exposed to the bird flu, as did the chickens, the study found.

Traditional killed-virus vaccines -- like the polio and seasonal flu vaccines -- trigger the body to produce infection-fighting proteins called antibodies.

Gambotto's bird flu vaccine also activated another arm of the immune system that uses white blood cells called T-cells -- in addition to antibodies -- to destroy foreign invaders.

By stimulating production of T-cells, which take longer for viruses to escape, the vaccine gave the body a second powerful weapon to potentially defend against many strains of bird flu, Gambotto said.

"Using this technology we can have much broader protection, which is important because the virus is always changing," said Gambotto, whose study appeared online yesterday in the Journal of Virology.

Baumgarth cautioned that many questions about Gambotto's vaccine remain unanswered: Will it work in the event of a real pandemic? Will it provide protection in people? If so, for how long? How long would it take to ramp up production?

Another potential caveat is that Gambotto's vaccine might not work in people previously exposed to some common colds.

Gambotto expects to learn next week whether his team will receive NIH funding to begin preliminary clinical trials to test the safety of their vaccine in 72 volunteers and start addressing some of these issues.

"Bird flu is something we should be prepared for, but even if a pandemic never happens, everything we learn now from this vaccine can be applied to vaccines for other emerging infectious diseases," Gambotto said.

Understanding Avian Influenza