Our work on Bird Flu

Avian Influenza, what we’re doing in the lab…

Brief Description
Since December 2004, the World Health Organisation (WHO) has recorded 132 deaths from the Avian Influenza virus (‘bird flu’) WHO ranks the current pandemic as a ‘Phase Three’ with low risk to humans. The greatest threat from this particular influenza virus is potential mutation into a highly infectious human strain, which could easily lead to a global epidemic.  A team of  Burnet researchers, led by Associate Professor Rose French, Head of Viral Immunology and Program Leader,  Vaccine Development, is investigating a number of new rapid diagnostics testing kits using yeast.

Australia is free of the current avian influenza, but globally 200 human infections were reported with mortality rates of 60 percent. Once exposed to the virus, signs and symptoms of avian influenza in humans are similar to those of conventional influenza (flu) with patients developing coughs, fevers, sore throat and muscle aches. The current outbreak is of avian Influenza type A H5N1 strain of the common virus, which usually affects birds and, more rarely, pigs and humans.

Influenza A viruses are divided into subtypes based on two surface proteins - Hemagglutinin (HA) and Neuraminidase (NA) that can combine to form a number of species specific subtypes.  The influenza virus is in a constant state of flux with small changes constantly occurring to the genetic material resulting in new strains.

The source of the H5 virus is thought to be wild waterfowl, which naturally carry many influenza strains, and usually cause no harm to humans. Once transferred from wild waterfowl to domestic poultry, the virus mutates, within months into the highly pathogenic strain that has already killed150 million birds worldwide. This increase in transmissibility from wild to domestic birds has been linked to the major flyways of migrating birds. In their search for water, some species of migratory waterfowl, through their annual migration, are spreading the virus into new geographical areas.

Since the first reported case of human infection in 2003 a total of 8 Asian nations have all reported human morbidity, they include: Viet Nam, Thailand, Cambodia, Indonesia, the Republic of Korea, China and the Lao People’s Democratic Republic. As the virus spreads along migratory routes, the Russian Federation, Mongolia and Kazakhstan were the first non-Asian countries to report cases of human infection. By October 2005, Turkey, Croatia and Romania had all reported their own outbreaks. The virus reached Ukraine at the end of 2005, with outbreaks in domestic fowl.

The highly contagious nature of avian influenza results in easy transmission from farm to farm via the movement of live birds, people via their shoes/clothes, contaminated feed, cages and vehicles. Low temperatures can also increase the highly pathogenic state of the virus.

Avian to human transmission of the H5N1 virus can occur in several ways, such as:

• human contact with infected live fowl and  poultry, by inhaling the airborne virus or  via exposure to droppings, saliva, nasal secretions and feathers
• human contact with diseased or dead domestic and or migrating fowl, particularly chickens, ducks, ducks and turkeys
• de-feathering and butchering of fowl/birds
• contact with and ingestion of raw or poorly prepared poultry and or waterfowl
• exposure to infected poultry and poultry by products such as eggs at open-air markets, at social gatherings, such as illegal cock fights
• exposure to contaminated land and or living within migratory route

The cultural practices in South East Asia of keeping small backyard flocks of chicken and ducks have facilitated the rapid spread of the disease, and increased human infection. Domestic birds are allowed to enter the household and often share living space with children and their families. Such birds are the prime source of income and food, even when signs of death or illness occur in a flock.

To reduce the spread of the virus in infected areas a number of containment practices are implemented, such as mass culling of infected birds, restricted movement of poultry within and between farms, strict decontamination and increased sanitary control.  There are two main implications to public and human health surrounding the current avian influenza outbreak. Firstly the increase in the number of reported cases of poultry to human transmission, with over 50% of humans infected dying .  H5N1 follows a rapid deterioration process in humans, causing multiple organ failure in previously healthy children, young adults and the elderly. The second and most serious risk is that given time, the genetic makeup of the virus would change, swapping genes indiscriminately and combining with a human flu virus, thereby creating a deadly new virus.

The threat of a human pandemic of avian influenza appears to be increasing. Members of the Burnet’s Vaccine Program have been successfully obtained five new research grants from the Australian Research Council and the National Health and Medical Research Council (NHMRC) to fund several avian influenza projects. 

Associate Professor David Anderson and his team are developing a number of rapid, point-of-care diagnostic tests. By examining patient’s samples, they are trying to identify the highly pathogenic strains of the human influenza A strain from the common, harmless strain. This project builds on Burnet’s successful partnership with Select Vaccines Ltd in the development and commercialisation of rapid, point of care diagnostic tests for hepatitis E and hepatitis A viruses.

The same principles of these world-first hepatitis tests, together with unique reagents against influenza, are being used to develop tests that will allow the rapid discrimination between conventional, human strains of influenza A (currently H1 and H3 strains) and the highly pathogenic H5 (avian) strain that is causing high fatality rate, particularly in South East Asia. Such tests will assist the timely management, treatment and (where necessary) isolation of patients with suspected influenza.

In another collaboration with Select Vaccines Ltd, Burnet scientist are using proprietary virus-like particle (VLP) system based on duck hepatitis B virus to produce candidate vaccines against influenza, including both human (H1 and H3) and avian (H5) types of the major viral protein, haemagglutinin. If successful, this approach would allow an influenza vaccine to be produced in vast amounts by fermentation in yeast or other industrial biotechnology processes, rather than the current production in eggs which is limited by supply, complexity and the highly pathogenic nature of some avian influenza viruses.

Associate Professor Ffrench is leading a study into individuals who have been previously infected with human influenza strains or recently vaccinated with current vaccine strains and show immune responses that cross-react with avian influenza strains. Blood is taken from volunteers and tested for reactivity with peptides representing the surface HA molecule of avian influenza (H5). We have already seen evidence of different types of immunity (heterotypic), which may be useful in creating new vaccine strategies that will protect us against a pandemic of avian influenza.

Current vaccines for influenza which are delivered by injection are not efficient at inducing a mucosal response. An ideal vaccine would comprise an antigen combined with a suitable adjuvant which could be administered intranasally or orally stimulating mucosal immunity.

Burnet scientists have found that a sugar (mannan) isolated from yeast when linked to various proteins and given intranasally can induce antibody at mucosal sites in mice. We have shown that these responses can be generated to viruses and bacteria. We will utilise mannan complexes of the whole inactivated influenza virus to ascertain if a virus neutralising antibody responses can be generated in the lung of mice. If these responses are able to protect mice from the flu virus we will use an altered form of bird flu virus to see if similar responses can be generated.

The new avian influenza vaccines which are heat stable and easy to administer are urgently needed to help protect Australia’s poultry industry.  The Burnet Institute, University of Melbourne, Monash University and Dow AgroSciences are involved in an Australian Red Cross linkage project grant working on the hypothesis that an oral, plant-made, avian influenza vaccine will protect chickens from disease.

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