Vaccine gives “100 percent” bird flu protection in animal study
Courtesy The University of Pittsburgh
and World Science staff
Researchers say they have genetically engineered an avian flu vaccine that completely protected mice and chickens from
infection in a study.
The scientists, from the University of Pittsburgh, Penn., said they built the vaccine from bits of the deadly H5N1 strain of the virus.
Avian flu has devastated bird populations in Southeast Asia and Europe and so far has killed more than 80 people.
Because this vaccine contains a live virus, it may stimulate the immune system better than vaccines prepared by traditional methods, say the researchers. Furthermore, because it is grown in cells, it can be produced much more quickly than traditional
vaccines, they say.
Thus the vaccine could be used to prevent the spread of the virus in domestic livestock and, potentially, in humans, according to the study, published in the Feb 15 issue of the
Journal of Virology.
“The results of this animal trial are very promising, not only because our vaccine completely protected animals that otherwise would have died, but also because we found that one form of the vaccine stimulates several lines of immunity against H5N1,” said
the university’s Andrea Gambotto, lead author of the study.
Gambotto and his colleagues constructed the vaccine by genetically engineering a common cold virus, called adenovirus, to carry either all or parts of an avian influenza molecule called hemagglutinin on its surface.
Found on the surface of all influenza viruses, this protein molecule allows the virus to attach to an infected cell and thereby to sicken and kill patients.
Since the late 1990s, outbreaks of the avian influenza H5N1 in poultry have occurred in Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand and Vietnam. Outbreaks recently have been reported in Turkey and Romania.
To date, H5N1 has caused the most large-scale and widespread bird deaths in known history—an estimated 150 to 200 million birds have either died in the outbreaks or been killed as part of infection control actions in the last eight years.
The H5N1 virus does not usually infect humans. But nine years ago, the first case of spread from a bird to a human occurred in Hong Kong during an outbreak of bird flu in poultry. The virus caused severe respiratory illness in 18 people, six of whom died. Since that time, more than 170 cases of known H5N1 infection have occurred among humans worldwide, approximately half of whom died.
Based on published genetic sequences of H5N1, the researchers, led by Wentao Gao, built several adenovirus “vectors.” These are viruses modified to serve as a delivery vehicle for foreign genes or DNA. The vectors contained genes conding for the hemagglutinin protein or parts of it.
The vectors protected mice against the deadly infection, so that they experienced only mild, temporary weight loss in response to it, they found.
Moreover, they reported that all of the animals immunized with full-length HA or the subunit vaccines developed strong cellular immune responses.
The vaccine “can stimulate several lines of defense against the H5N1 virus, giving it greater therapeutic value,” said the university’s Simon Barratt-Boyes. “More importantly, it suggests that even if H5N1 mutates, the vaccine is still likely to be effective against it. How effective, we are not sure.”
Working with the U.S. Department of Agriculture, the researchers also tested its effectiveness in chickens, almost all
of which normally die when exposed to H5N1. The researchers inoculated four groups of chickens, then gave them doses of whole H5N1 virus 10,000 times greater than the dose given to the mice and significantly greater than what farm chickens are likely to be exposed to during a natural outbreak.
All the chickens immunized through under-the-skin injections survived exposure to H5N1, developed strong immune responses and showed no clinical signs of disease, the researchers found. But chickens that received the vaccine through another method—through the nose—died in about half of cases.
Widespread inoculation of susceptible poultry populations could provide a significant barrier to the spread of the virus, the researchers said. Also, if there were a disruption in the traditional vaccine production pipeline, a recombinant vaccine could be an attractive alternative for human immunization as well.
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