A vaccine to prevent flystrike on sheep
Industry Issue:
The Australian sheep blowfly (Lucilia cuprina) causes flystrike in sheep and is one of the most significant economic and welfare threats to the Australian and New Zealand sheep industries, incurring annual control and lost production costs in the vicinity of $170 million and $50 million, respectively. Flystrike results in major welfare issues for the animal, severe degradation of the fleece, impact on meat quality and in severe cases, death of the animal.
Control of this parasite has been a long term problem for the sheep wool and meat industry and there are a number of issues associated with its control. Current control measures for this pest have principally relied on seasonal and repeat insecticide treatments and surgical intervention whereby skin is surgically removed from the breech of a lamb in a procedure termed mulesing. Skin clips, chemical treatment of the skin and wool follicles around the breech, and breeding strategies have all been developed and used to varying degrees of uptake and success.
Figure 1: Flystrike is caused by the Sheep blowfly (Lucilia cuprina). Diagram shows lifecycle and the effect of flystrike on sheep.
The industry is desperately in the need of an effective, welfare friendly, consumer accepted and cost-effective alternative flystrike control and prevention technology. A flystrike vaccine will help fulfil these industry requirements as a key part of an integrated pest management approach.
The solution:
CSIRO is proud to partner with Australian Wool Innovation in a project aiming to develop a Flystrike Vaccine for the Australian sheep and wool industries. A flystrike vaccine represents an ecologically- and animal welfare-friendly control measure that has no chemical residues and has the potential for long term and cost efficient flystrike control. Vaccine technology is widely accepted by the public and is a method of control that can have an immediate positive effect and offers a paradigm changing solution to the industry problem.
The Flystrike Vaccine project is into its second year of research with CSIRO developing close collaborations with the University of Melbourne (Perry and Anstead Group), Griffith University (Kolarich Glycomics Group) and the University of Queensland Protein Expression Facility. The respective expertise available in this collaboration is helping progress this initiative.
Key Project objectives are to:
- Identify a pipeline for antigen identification and production.
- Produce prioritised vaccine antigens as recombinant proteins in bacteria, yeast or insect cell systems or by chemical synthesis.
- Test recombinant protein antigens in prototype vaccines in sheep trials.
- Identify vaccine antigens that induce strong immune responses in sheep and
- produce inhibition of Lucilia cuprina larval growth in vitro.
- Identify lead vaccine antigens to progress to testing and commercial development of a flystrike vaccine with an Animal Health Veterinary Pharmaceutical partner.
Figure 2: A) Electron micrograph of Sheep blowfly larval gut showing impaired gut permeability caused by antibodies raised in sheep following injection of a prototype vaccine. B) Larvae (right of frame) fed on sera from vaccinated sheep displaying impaired growth compared to larvae fed normal sheep sera (left of frame). C) Transcriptomics analysis has been used to identify lead antigens from key larval lifestages and organs which are now being tested as prototype recombinant vaccines.
Vaccine trials in sheep are currently underway to testing prototype vaccines with more research and testing still to be done.
Lead candidate antigens representing key protein classes identified from the tissue and lifestage gene expression analyses are being tested as prototype vaccines. These antigens have been engineered and produced as proteins using recombinant molecular technologies utilising either Bacteria or Insect Cells as “protein production factories”. These proteins are formulated with adjuvants to produce prototype vaccines and are tested in sheep. Immune sera are collected from vaccinated sheep during the trial and assayed for immunological response and ability to confer protection from flystrike initiation and larval growth.
Figure 3: Key steps in the process of engineering and formulation of candidate antigens for prototype vaccine production and testing. Steps involve engineering the candidate gene encoding the protein target of the vaccine, cloning it into bacteria or insect cells, culturing the cells to produce the recombinant protein/antigen, purifying the antigen, formulating it with an adjuvant and administering it to sheep which are then assessed for antibody titre response to the vaccine and larval growth effects measured using ex-vivo growth bioassays.
Sheep immunological studies have also been undertaken to investigate immunological response of sheep to control antigens simulating a flystrike vaccine. This is informing the effect of vaccine dose, longevity of the immunological response and is assisting with formulation of the trial flystrike vaccines. Studies in collaboration with Griffith University Glycomic’s Institute are underway to investigate the chemical synthesis and modification of vaccine antigens to modulate and improve the immune response of sheep to the vaccines.
The Flystrike Vaccine project is in the process of further refining and testing of lead vaccine antigens with the aim to deliver a validated short-list of candidate antigens that when formulated into prototype vaccines prevent or inhibit flystrike establishment and larval growth. Information garnered from this project will help inform future research into flystrike vaccine development. CSIRO will continue to work together with collaborators to further refine candidate antigen selection, design and production.
Strong interest has been shown from VetPharma companies and once a validated short-list of candidate antigens is identified, discussions with a commercial partner will be progressed with the key aim of commercial development of a flystrike vaccine.
This CSIRO project involves a dedicated team of scientists and technical specialists coordinating and working across key research sites at St. Lucia and at Chiswick, Armidale. Molecular laboratories, collaborations and field research facilities are key to enabling the progress of the Flystrike Vaccine research project.
Figure 5: CSIRO research team undertaking tasks associated with flystrike vaccine development.
Team members:
Graham Acton (Livestock specialist)
Neil Bagnall (Technical specialist)
Suzie Briscoe (Technical specialist)
Duncan Elks (Livestock specialist)
Jody McNally (Technical specialist)
Tony Vuocolo (Scientist and Project Leader)
Acknowledgements:
Brad Hine, Peter Hunt, Andrew Kotze and Aaron Ingham
Further information:
Tony Vuocolo
Flystrike Vaccine Project Leader
CSIRO Agriculture and Food
Livestock and Aquaculture Program
Queenland Bioscience Precinct,306 Carmody Rd,
St. Lucia, 4067, Brisbane, Australia
tony.vuocolo@csiro.au
+61 7 3214 2693