Scientists are testing vaccines to defeat flystrike

Scientists are testing vaccines to defeat flystrike

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Scientists believe they are closing in on a commercial vaccine for flystrike.

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TESTING TIME: CSIRO project leader Tony Vuocolo injects a prototype vaccine into sheep. Picture: AWI.

TESTING TIME: CSIRO project leader Tony Vuocolo injects a prototype vaccine into sheep. Picture: AWI.

Scientists believe they are closing in on a commercial vaccine for flystrike.

Prototype vaccines have already been developed half way through a four-year $2.5 million research project between the wool industry and CSIRO.

A potential vaccine against flystrike has been the subject of decades of research work.

Blowfly infestation of sheep wool, skin and tissue results in an estimated $280 million losses to the wool industry.

CSIRO researchers have identified key proteins in blowfly maggots which are important for their growth and development.

The team has developed and tested prototype flystrike vaccines that help the sheep's immune system build a defence mechanism (antibodies) that will target and destroy these proteins.

However, extracting natural larval protein from actual flies for the vaccine is prohibitively expensive commercially, so the team is continuing to look at ways to develop an alternative and cheaper way to synthesise them.

The dream of developing a vaccine gained focus through almost a decade of research at the University of Melbourne which culminated in the mapping of the fly's full genome in 2015 after three years of work.

This $2.5 million collaborative project with Australian Wool Innovation has achieved much in its first two years.

CSIRO project leader Tony Vuocolo said the sheep blowie, Lucilia cuprina, was a formidable adversary.

Vaccines have been designed, produced and tested during the past 18 months with more in the pipeline.

Twenty-six different formulations of vaccine have been tested in sheep as well as in a variety of laboratory tests.

"Whilst a potential commercial vaccine is still a way down the track," Dr Vuocolo said, "CSIRO's results indicate they can produce high antibody levels in sheep against the blowfly."

Antibodies are the defence molecules, akin to 'bullets' in general terms, produced by the sheep against the blowfly maggots.

The major challenge faced is producing these 'bullets' in a form that will specifically hit the maggots in vulnerable spots and be powerful and plentiful enough to penetrate and ultimately over-run the maggots' armour-like protection.

The blowfly proteins, called antigens, used in the prototype vaccines to generate the immune response in sheep against the blowfly are being produced using several different production systems.

These include:

  • isolation of proteins directly from blowfly larvae/maggots, also known as native antigens,
  • production of blowfly proteins in bacteria,
  • production of blowfly proteins in specially adapted insect cells.

In the last two cases, the proteins are artificially produced and are called recombinant antigens.

It has already been demonstrated some native blowfly antigens used in the vaccine are effective in producing an immune response in sheep that results in stunting of maggot growth and in some cases the immune response of the sheep results in the death of the blowfly maggot when they feed on the sheep serum.

Serum is the component of blood that contains the antibodies.

Unfortunately producing a commercial vaccine through this approach using native antigens is not viable and that is the motivation for production of the blowfly antigens in bacteria or insect cells, and more recently by chemical synthesis.

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The difficulty of the artificial production of blowfly antigens is being able to produce antigens in a form which replicates the precise three-dimensional structure of the native blowfly antigens.

This is more easily performed with proteins that have simple structures but more difficult with complex proteins.

CSIRO will continue to progress flystrike vaccine development during the next year.

In the absence of a sheep blowfly cell line to artificially produce the vaccine antigens, CSIRO researchers will use the next best resource and test and validate a newly established fly-related cell line to produce vaccine antigens.

CSIRO is partnering with the University of Queensland Protein Expression Facility to undertake this work.

It is envisaged this will assist in producing flystrike vaccine antigens that better resemble the native blowfly proteins.

CSIRO will continue to work with the University of Melbourne (UoM) flystrike team cross-referencing vaccine antigens with sheep blowfly population genome studies that UoM have performed.

This provides information about blowfly population genetics and how this might impact vaccine design and optimisation for different Australian regions where the blowfly is found.

A collaboration with Griffith University Glycomics Institute is providing a clearer insight into the sugar structures found on the native blowfly proteins and is providing the opportunity to design and develop synthetic vaccines.

These synthetic vaccines will be tested and if successful have the potential to bypass cell-based antigen production systems.

A study examining vaccine dose and the length of protection is nearing completion and is informing how CSIRO will formulate the future flystrike vaccine and how long the protective antibodies are maintained in the sheep.

The ideal aim is to produce a vaccine that requires a single annual dose just before peak fly season.

"CSIRO remains confident that if the right vaccine antigen production systems can be developed then an effective vaccine can be developed that strikes back at flystrike," Dr Vuocolo said.

Developing a pipeline for vaccine engineering and production is the key limiting factor if we are to be successful in development of a flystrike vaccine.

"Overall, the next year will produce a strong statement on whether the development of a flystrike vaccine will ultimately be achieved.

"CSIRO remains confident that if the right vaccine antigen production systems can be developed then an effective vaccine can be developed that strikes back at flystrike."

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