Researchers using donut-shaped molecules to make a new bird flu vaccine

14 Mar 2018
Professor Linda Lua
Professor Linda Lua

Professor Linda Lua, Director of the Protein Expression Facility housed at AIBN, is developing a new vaccine candidate for avian influenza.

Influenza in birds represents a significant biosecurity risk for a human pandemic, as well as a major risk for poultry industries. Forms of avian influenza, such as H5N1 and H7N9, can spread rapidly in poultry flocks and some strains already have the capacity to infect humans. For example, hundreds of cases of H5N1 in humans have occurred from close contact with infected birds, with a fatality rate of 60%.

Avian influenza has been detected in bird populations in 77 countries so far, necessitating the culling of millions of domestic birds. The threat of the next avian influenza outbreak is ever present, says Professor Lua.

“It’s really a matter of when.”

 “Vaccination in poultry can reduce the spread of influenza within poultry populations,” says Lua. “This can protect poultry industry in Australia during an outbreak.”

“Containing the spread of avian influenza in poultry can also reduce the risk to humans.”

She explains that one problem is that current influenza vaccines are not easy to make quickly. To address this, Lua and her colleagues designed a ‘capsomere’ platform.

A protein called haemagglutinin usually sits on the surface of influenza viruses, and this can vary quite a lot between strains. Lua and her colleagues took part of this protein from an avian influenza virus and attached it to a specially designed protein called VP1. When five of these VP1 proteins link together in a ring, they form a ‘capsomere’.

The resulting donut-shaped capsomere is non-infectious, but because it displays parts of the virus protein, it trains the bird’s immune system to fight a real influenza infection. Recent tests of the avian influenza capsomere vaccine show that it prevents the illness in poultry.

“The immunised chickens are protected and they survived when exposed to the real avian influenza virus,” says Lua.

The way the capsomere vaccines are produced provide another advantage. Currently influenza vaccines take six to nine months to be manufactured in large enough volumes. Such lag times make it precariously difficult to respond to an outbreak.

Moreover, vaccines are normally grown in chicken embryonated eggs and while this growth process is slow, it works well for a number of other diseases. However, avian influenza doesn’t just harm birds, it harms the embryos inside the eggs as well, making this form of vaccine production problematic.

By contrast, the capsomere production method uses bacteria to make the protein components, enabling high volumes to be made.

“We use an E coli bacteria cell factory to produce the proteins that self-assemble into capsomeres inside the bacteria, and extract the proteins, said Lua. “This way we can make them quickly and cheaply.”

It’s an efficient and powerful approach for mass-manufacture, and the resulting vaccine is potentially less than 10 cents per dose.

The major advantage of the capsomere platform is its speed. The capsomeres can be quickly tailored to match circulating viruses, then large volumes of the new vaccine can be produced within weeks, enabling swift vaccination responses to prevent an outbreak. By preventing avian influenza from circulating within bird populations, this would also substantially lower the risk of the emergence of pandemic avian influenza in humans.

More information on Professor Lua’s research on avian influenza vaccines can be found in the journal Vaccine.

More about Avian Influenza and Human Pandemics

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses
Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green). 

Every year millions of people around the world are infected with seasonal influenza. While many endure a moderate respiratory illness as a result, for others it’s much more serious. According to the World Health Organization, 3 to 5 million people experience a severe influenza infection, leading to between 250,000 and 500,000 deaths.

Pandemic influenza presents an even greater threat. Although pandemic influenza epidemics occur less often than seasonal epidemics, they exact a substantially higher death toll. The ‘Spanish Flu’ influenza pandemic of 1918 infected around one third of the world’s population at the time and killed around 50 million people.

Such pandemics arise when a virulent new strain of influenza emerges. Because the human population hasn’t been exposed to the strain before, immunity is low, allowing rapid infection and transmission.

How does a new pandemic strain emerge? Certain types of influenza are zoonoses, meaning they can infect animals — such as birds, pigs, and bats — as well as humans. Those animals can act as reservoirs for influenza viruses, which then circulate within their populations. The main problem is that influenza is something of a shape-shifter, meaning it can undergo rapid genetic changes. Some of these changes allow an animal influenza strain to infect humans, other changes enable a virus to not only become highly contagious between humans, but to also become extremely lethal.

Preventing influenza circulation within animal populations is both beneficial to those animals as well as humans.

Media: communications@aibn.uq.edu.au; Professor Linda Lua, l.lua@uq.edu.au, +61 7 3346 3979.

Latest