TOKYO--While a killer avian influenza decimates poultry flocks in Asia, scientists have started work on a vaccine to protect humans from the deadly disease. Because this virus stymies traditional approaches, they are using a novel technique to hatch a tame virus. But a flu vaccine produced with this kind of genetic modification has never been used in humans, raising questions about safety and efficacy.
Since last December, the H5N1 strain of avian influenza has appeared in at least eight Asian countries. Human infections are rare and so far appear to result from direct exposure to diseased birds. But researchers worry that if the virus infects a person already carrying a human flu, it will reassort into a new virus easily transmissible from person to person, touching off a global pandemic. The World Health Organization (WHO) hopes to make a vaccine to prevent rare human deaths from bird flu and also help prevent this potentially devastating viral reassortment. If the virus does acquire human transmissibility, however, yet another new vaccine may be required.
Traditional flu vaccine development relies on mixing the target flu virus and a harmless flu strain in chicken eggs and then screening for an appropriate vaccine candidate. This doesn't work for H5N1 because it kills chicken embryos. To sidestep this problem, a group at St. Jude Children's Research Hospital, Memphis, Tennessee, one of the WHO collaborating centers, using a technique called reverse genetics. Working with a H5N1 strain that briefly appeared in Hong Kong in 2003, the researchers cloned the two genes that code for the virus's surface glycoproteins. Then they added six more genes from a "safe" influenza virus strain long used in vaccines. The resultant virus can't cause disease but carries the surface glycoproteins that stimulate the immune system to produce antibodies to H5N1.
Unfortunately, the H5N1 strain circulating this year differs so dramatically from the 2003 strain that a new vaccine is needed. Producing it will take until at least late February, according to WHO officials. And that's not the only obstacle. WHO's Klaus Stöhr worries that some countries may object to a vaccine based on a genetically modified organism. Another challenge is that MedImmune Inc. of Gaithersburg, Maryland, holds the patent for the reverse genetics process. Although company spokeswoman Jamie Lacey says the firm offered "to license our patent rights to the manufacturers of a pandemic vaccine," details remain to be negotiated. A final issue is how quickly drug manufacturers can ramp up mass production.