Parasite glycoproteomics and vaccine development

Better understanding of parasite glycoproteins is enabling us to develop better vaccine antigens. This promotes better protective immunological responses making animals more resilient to parasite threats.

The Flystrike Vaccine project team led by Tony Vuocolo, supported by funding from Australian Wool Innovation (AWI) along with Edward Kerr, an early career scientist with the CSIRO Immune Resilience FSP have recently performed the first reported analysis of the complex glycoproteome of the Australian sheep blowfly.

This project is developing CSIRO’s glycomics and glycoproteomics capability and applying it to develop an understanding of parasite glycoproteins on animal immune responses and vaccine development.

What is glycomics and glycoproteomics?

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.

This new understanding of glycosylation processes in the blowfly are being used to help inform further flystrike vaccine development by the Flystrike vaccine team and the Immune Resilience Future Science Platform.

Innovation in this area is also being applied to research on other parasites of livestock, fish and human red meat allergy caused by paralysis ticks.