R&D: Tick vaccine using genomics to make encouraging progress

Jon Condon, 18/01/2013

While there is still some way to go to a commercial release of a long-acting tick vaccine product in Australia, industry stakeholders came away optimistic about the prospects following an R&D update on progress recently in Brisbane.

Estimates suggest the Australian cattle industry suffers productivity losses worth $175 million each year due to the impact of ticks and tick-borne diseases, and costs of treatment to ensure compliance with regulatory protocols for interstate and export livestock movement.

The high costs associated with controlling ticks in Australia and internationally, together with the impact of the use of chemical controls on food safety and the environment, have meant the cattle industry and governments worldwide have identified the development of a tick vaccine delivering 12 month's immunity and 90 percent efficacy as a high priority.

But is there high producer demand for a once-a-year, effective tick vaccine?

An earlier MLA market demand, cost/benefit review carried out by Matt Playford in 2006 showed that producers themselves in ticky country were not ‘frequently bringing the topic up’, unless prompted. But that result had to be kept in context, MLA northern R&D manager Wayne Hall argues.

“We interpreted that result to mean that most northern producers were living with ticks, using Brahman cattle, and to them, it was not a significant issue.”

“But with the more recent drive towards better meat quality and MSA programs, producers in those areas are increasingly looking at what can be done to get away from purebred Brahman cattle. It’s there where the vaccine demand will come from, and it will be significant,” Mr Hall said.  

The recent Brisbane stakeholder gathering was told a once-a year treatment tick vaccine might be around two years away from a commercialisation phase.

Delivering a presentation was research scientist Dr Ala Lew-Tabor, a senior research fellow with Queensland Alliance for Agriculture and Food Innovation (QAAFI), a joint alliance between the University of Queensland and Queensland DPI.  

Looking back, Australia had access to a recombinant tick vaccine product, Tickgard, (based on the Boophilus microplus Bm86 gut antigen) which was commercially released by Biotech in Australia in 1994.

Effectiveness in tick reduction was around 81pc, Dr Lew-Tabor said, but that was under optimum re-treatment conditions.

The product never sold more than 250,000 doses a year into the beef and dairy industries, due to cost and the need for multi-dose treatment over several months to provide protection.

At that point the vaccine product disappeared off the market for several years, before re-introduction in 2002, at a higher cost, and targeted mostly at dairy producers. Production ceased around 2004.

The efficacy of the old recombinant BM86 vaccine varied widely, according to studies in different countries. Under heavily-controlled Cuban Government vaccination programs, studies suggested an 86pc reduction in cattle tick, and 82pc reduction in the use of tick control chemicals (acaricides), and reduced tick fever over a period of eight years.

However it appeared to work much less effectively in Argentina, Brazil and Australia than it does in Cuba. Additionally, the Cuban trials appeared to achieve quite high protection with just two shots, followed by an annual booster, whereas the common view in Australia and elsewhere is that three or four yearly doses were necessary to maintain protection. The reasons for this have not yet been explored, Dr Lew-Tabor said.

Genomic approach to tick vaccine development  

Under the now-concluded Beef CRC program, new research started into ways to develop a tick vaccine that:

  • had long-lasting effectiveness
  • was effective across a number of tick species (important for international use where other tick species exist)
  • was cheap enough to encourage commercial use, and
  • was effective across multiple stages of the tick life cycle.
  • The benchmark set by the industry was 90 percent efficacy, and requiring only one annual vaccination.

“The original Tickgard product was developed in the 1980s in the conventional way of trying to identify an active protein in a cocktail of proteins using a slow filtering process,” Dr Lew-Tabor said.

“But by starting with the whole genome of a particular organism, it is possible to screen everything, using several methods of computer analysis. The well-known human and cattle genome projects mean there are now so many predictive algorithms that can be used to assist this work,” she said.

Using this novel genomic science approach that has not been carried out anywhere else in the world, researchers have started to pinpoint tick vaccine antigens that will enable cattle to better resist tick challenge.

“One of the challenges is that the cattle tick genome is in fact more than twice the size of the human genome, full of ‘repeat non-coding stuff’ that makes it more difficult to distinguish candidate genes from,” Dr Lew-Tabor said.

“That meant it was impossible to do an entire genome project, so what we started with was a database held by the US Department of Agriculture that held 16,000 gene sequences,” she said. Added to this was a little local gene discovery work.

Researchers identified 400 possible antigen genes, targeting the larval stage and female ticks.
Screening and testing targeted the best 95 candidates, including those that might bind antibodies and had an effect at more than one lifecycle stage. About nine of the best performers were identified, and used in a series of trials.

The best vaccine antigens produce an immune response in the beast which interferes with tick attachment and feeding and the ability of surviving ticks to lay eggs.

A cocktail of about six of the best peptides were trialled in animals, resulting in a drop in tick numbers by around 87pc. A second, single poly-peptide produced lesser protection at 42pc, and another single antigen produced a 49pc tick reduction.

Dr Lew-Tabor stressed that these results were not achieved with a ‘fully-optimised’ final vaccine product with antivent, or delivery/dose work, but were the result more of a small ‘look, see’ experiment. Nevertheless, the result was highly encouraging.

Current research is focussing on finishing the screening process on individual peptides, and look more closely at blends that might produce even better outcomes.

The ultimate aim is to define an attractive package of peptides that can then be taken to a pharmaceutical company for commercialisation.

Asked what the expected timeline might be to get there, Dr Lew-Tabor suggested two years, provided the required trial work could be done, given limitations over access to shared trial facilities.

Once potential vaccine candidates are licensed to a pharmaceutical company to develop into a commercial vaccine, it may still take some years to complete registration requirements for use in Australia and overseas, however.

Separate, unrelated research work is looking at improving the performance of the original BM86 gut antigen used in Tickgard, by turning it into a single-dose product. This project started last July under a Queensland – Smart Future funding grant. The project is based around a novel delivery platform developed through the Polymer CRC work.

Trials will start this year.




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