CSIRO, Imugene cooperate on bird flu vaccine project

By Graeme O'Neill
Thursday, 05 February, 2004

CSIRO Livestock Industries and its animal health spin-off Imugene (ASX:IMU) have begun a joint research project to develop a vaccine to protect chickens against the deadly new strain of avian influenza devastating poultry farms in Asia.

The project aims to have a prototype vaccine for the latest strain of the H5N1 serotype within months, based on Imugene's proprietary Adenoviral Vector Delivery System (AVDS), which was developed by CSIRO Livestock Industry researchers.

"If we pull out all the stops, it could take as little as three months," said Dr Chris Prideaux, of CSIRO's Australian Animal Health Laboratory (AAHL) in Geelong.

Even though a new vaccine would probably come too late to have an impact on the Asian bird flu epidemic, Prideaux said the AVDS technology could be quickly adapted to protect Australia's poultry industry against new, emergent strains of avian influenza.

AVDS technology employs attenuated strains of adenovirus that can be genetically modified to introduce genes for new antigens from pathogenic viruses -- in the case of the new strain of bird flu, the haemagglutinin antigen (HA), one of the two antigens that forms the coat of the virus.

Prideaux said it would take time to identify and characterise the HA antigen from the new virus. "We don't know if all of the outbreaks in Asia are caused by the same strain, or whether there has been antigenic drift from region to region," he said. "However, we'll pick the most prominent strain, and expect it to provide good cross-protection against other new variants of the H5N1 serotype."

Prideaux said if the project were successful in developing an effective prototype poultry vaccine, the antigens would be made available to laboratories attempting to develop a human vaccine against the bird flu.

He said safe human adenovirus vectors were already available to express the HA antigen for a human vaccine -- they had been developed for gene therapy experiments.

Prideaux said such vaccines would be safer for human use than traditional attenuated-virus influenza vaccines, because they used isolated antigens, rather than the entire influenza virus.

Vaccine manufacturers had not gone down this route, because of concerns that in the current climate of community apprehension about genetically modified organisms (GMOs), the community would reject a vaccine based on a GM virus.

Alternatives

The US Food and Drug Administration is seeking alternative ways for mass-producing new vaccines that do not rely on injecting attenuated influenza viruses into embryonated chicken eggs -- the H5N1 strain is also lethal to chick embryos, which would complicate efforts to mass-produce a new vaccine.

Prideaux said that, in the event of a major human pandemic of bird flu, any concerns about GM vaccines would probably disappear very rapidly.

Despite quick action by the Australian Quarantine Inspection Service (AQIS) to reinforce surveillance at Australia's international airports to prevent the entry of infected poultry meat or eggs, migratory birds are the most likely route for the virulent H5N1 avian influenza strain's arrival in Australia.

Prideaux said there had been five outbreaks of avian influenza on Australian poultry farms since 1976, and in each, there was circumstantial or obvious evidence of contact with waterfowl. None of the outbreaks, which caused severe disease in chickens, involved the H5N1 serotype.

The most recent, on a poultry farm at Tamworth in 1997, involved a strain of the H7N4 serotype. There have been three outbreaks on Victorian poultry farms in Victoria -- 1976 and 1982 (both H7N7), and 1992 (H7N3), while a H7N3 strain also caused an outbreak in Queensland in 1994.

Prideaux said migratory birds were major vectors of influenza, but it was not possible to link the previous Australian outbreaks to the migration of particular species.

He said that Australia's tropical north, where there are few poultry farms, provided a barrier to epidemics, but poultry farmers were aware of the need for effective biocontainment to keep their flocks away from contact with waterbirds, and dams, ponds or lakes contaminated by waterbird faeces.

Devastating outbreaks of a H5N2 strain avian influenza on poultry farms in Pennsylvania in 1983-4, forced a cull of 18 million birds at a cost of $US60 million. Another H5N2 strain caused an outbreak in Mexico in 1993. Both were subsequently traced to infected ducks kept in close proximity to chickens in live poultry markets in each region -- the Mexican outbreak originated from the introduction of a single virus of the North American lineage.

Researchers have found that an H2N2 strain found in live ducks in US markets is antigenically related to the human strain that caused the Asian influenza pandemic in 1957 -- the strain has since disappeared from the human population, but persists in birds.

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