Parasite glycoproteomics and vaccine development
Edward Kerr is one of our early career scientist based in Brisbane and working within the Immune Resilience Future Science Platform. His FSP project is associated with a larger piece of work, the Australian Wool Innovation (AWI) funded Flystrike Vaccine project led by Tony Vuocolo.
Edward recently presented his initial research findings at the Beilstein Glyco-bioinformatic Symposium in Germany, and Edward and Tony also presented together at the Protein Australia Conference in Brisbane.
We caught up with Edward to find out how his work ties in with developing a vaccine against flystrike.
Edward’s FSP project is developing CSIRO’s glycomics and glycoproteomics capability and to develop an understanding of parasite glycoproteins on animal immune responses and vaccine development.
What is glycomics and glycoprotemics?
Glycomic studies investigate glycans, carbohydrate-based polymers made by all living organisms, that decorate proteins and modify their functions and structures.
While proteomics is the study of all proteins within a system, glycoproteomics lies at the intersection of glycomics and proteomics and is the study of the glycans present on all proteins within a system, including glycan compositions and locations.
Flystrike on sheep
Flystrike on sheep is a major sheep health and welfare problem in Australia caused by Lucilia cuprina (Australia sheep blowfly). The fly lays eggs on live sheep, and when the larvae hatch, they feed on the sheep causing physical damage, creating conditions conducive to secondary bacterial infections.
In Australia, the economic cost of flystrike in sheep is more than AU$320 million per year. This is due to production losses and the cost of prevention and control.
With the continued development of resistance to insecticides, a key approach is to develop a vaccine. The aim of a vaccine is to stimulate the sheep’s immune system to disrupt the growth of the parasite.
Flystrike vaccine project
Vaccines work by containing an antigen, which is often a protein, but is any substance that causes the immune system to begin to produce antibodies.
The Flystrike Vaccine Project has developed a prototype vaccine using proteins secreted from specialist cells of the blowfly’s anterior midgut as the antigen. The research is investigating both native antigens isolated from blowfly larvae and recombinant antigens produced in specialised insect cells which have been transformed to produce specific blowfly proteins.
In the first instance, the Flystrike vaccine team prepared the native protein antigen from a proteo-glycan matrix secreted to line the gut of blowfly larvae. Proteo-glycans are produced after a process called glycosylation, when a carbohydrate attaches to a target molecule.
When this form of the vaccine was tested, it showed up to a 75% per cent inhibition of larval growth in laboratory larval feeding and growth assays. Subsequent production of this native antigen using a different culture regime reduced this efficacy of the antigen in the vaccine to 20%.
Vaccine development is a complex science and optimising antigen production and properties is critical as has been observed in the Flystrike Vaccine project.
How glycoproteomics is helping
The reason for the difference in vaccine effectiveness may occur during the process of adding the glycans to the protein antigens when being produced in the larval gut cells. To study this, we must first gain a good understanding of the complex glycoproteome of the blowfly midgut lining.
Edward presented the first reported analysis of this at the conferences in Limberg and Brisbane.
This new understanding of glycosylation processes in the blowfly are being used to help inform further flystrike vaccine development by Edward and the Flystrike vaccine team.