A Vaccine Solution?
Scientists knew they were up against a formidable virus when they tried the time-tested way of making a vaccine to prevent bird flu. They injected the virus into fertilized chicken eggs to grow it, but instead the virus often killed the eggs.
Since 2000, virologists at St. Jude Children's Research Hospital in Memphis and elsewhere have been working on a new strategy to combat the deadly H5N1 flu virus. It's called reverse genetics, where the virus's genes are rearranged in a lab to make a new strain.
Influenza viruses are constantly evolving single-cell organisms, with eight genetic segments at their core that carry the instructions for replication. On their surface, they have two different types of protein spikes. One protein spike, the hemagglutinin (HA), makes a virus stick to a cell to cause infection. The other spike, neuraminidase (NA), allows newly formed viruses to leave the host's cells. When people are vaccinated against flu, the human immune system makes antibodies that recognize these surface protein spikes. Then, when a virus with the same types of spikes tries to cause infection, the antibodies attach to the invader's spikes and fight it off. Some flu subtypes, H5 and H7, can evolve into highly lethal viruses as they pass from animal to animal or on to humans, mixing their genetic material and forming new, highly transmittable strains.
"At the level of the genes, we now know why this H5N1 virus is so deadly," says Richard Webby, a virologist at St. Jude. "And with reverse genetics, we can go into the genetic material and remove the pieces of protein that cause those traits." To develop the H5N1 "seed strain" for making the first pandemic vaccine, the St. Jude lab took the surface protein spikes of the bird flu virus, the H5 and N1, and put them together with the genetic material of a harmless, master strain that's been used for decades to produce flu vaccine. But instead of allowing the genes of the two viruses to mix in a fertilized egg--a process called reassortment--"we're starting with the genes in a test tube and putting them together in the lab," says Webby. "It takes some of the randomness out of the vaccine process."
St. Jude's H5N1 strain has been used to make the first batches of investigational bird flu vaccine. Two companies, Sanofi-Aventis and Chiron, are each producing about 8,000 doses of it. Though Chiron is behind schedule, Sanofi-Aventis shipped its first doses in early March to the National Institute of Allergy and Infectious Diseases. NIAID announced last week that recruitment for human trials is beginning at three medical centers.
In these H5N1 vaccine trials, says Anthony Fauci, director of NIAID, researchers will determine the safety and correct dosage of the vaccine, as well as how volunteers of different ages react. "But there is no reason to believe this vaccine will be any less safe than any other flu vaccine," he says, though the vaccine may require two doses rather than the usual one. NIAID is also developing a live, weakened H5N1 vaccine, similar to FluMist, the nasal spray flu vaccine.
In the end, the actual production of vaccine may be the central problem in curbing a pandemic. Even if Sanofi's Pennsylvania plant, where H5N1 vaccine will be made, operates at full throttle, there would not be enough to vaccinate everyone in the United States, says NIAID's Fauci. In addition to the pilot lots, the United States contracted with Sanofi for an additional 2 million H5N1 doses. "This may seem inadequate," Fauci adds, but it should make it easier for Sanofi to rapidly make 30 to 40 million doses if needed. Whether that will be enough to stop a killer flu remains an open question.
This story appears in the April 4, 2005 print edition of U.S. News & World Report.
advertisement
