Ireland has joined the race to beat equine flu, which is looming over the Melbourne Cup, writes Claire O'Connell
Since August, an outbreak of equine influenza in Australia has infected more than 36,000 horses and cost the government there more than €70 million in financial aid. In addition, the microscopic virus currently looms large over the most famous event in Australia's equestrian calendar, this month's Melbourne Cup.
Now Irish researchers are joining in the race to develop a more effective vaccine against horse flu. Scientists from the Irish Equine Centre in Co Kildare have been using genetic tricks to create a weakened version of the live virus to build up immunity in horses without making them sick.
In Ireland, where the virus is endemic, vaccination of racehorses and competition horses is mandatory, says virologist Prof Anne Cullinane of the Equine Centre. "Vaccination decreases the risk of infection, clinical disease and virus shedding," she says.
To date, the majority of vaccines have used killed virus or parts of the virus structure to encourage an immune response in horses. The focus is now on developing a live vaccine because it mimics the natural process of infection and stimulates a better immune response, providing more effective cover.
That's why Prof Cullinane and researcher Dr Michelle Quinlivan have been working with Mount Sinai School of Medicine in New York on the first attempt to build a new, weakened version of the horse flu virus using "reverse genetics".
"Classically with genetics you start off with a trait like a physical abnormality and you try to figure out what the basis for it was. But in reverse genetics you start out with the DNA and you try and tweak or change it and see what happens when you do that," says Dr Quinlivan, who completed the work in Mount Sinai as part of her PhD, which was co-supervised by Prof Sean Arkins at the University of Limerick.
Dr Quinlivan took the genetic material of a flu virus, tweaked it and inserted it into cells in the lab. The cells became factories for making the new, designer viruses that were all bark but no bite. "We looked at how to weaken the flu virus so that it would be a good vaccine virus, because you don't want something that's going to make the horse sick," she says.
To create the weakened virus, she chopped up a gene it normally uses to defend itself against the host. If all went to plan, the new, altered virus could be easily killed off by the horse when used as a vaccine, explains Quinlivan, who received funding from Ircset.
But crucially, the weakened virus would still carry enough information for the horse's immune system to mount a good response to the vaccination. "They still have a foreign body in their system so they will still get antibodies and cell-mediated immunity," she says.
Her modified viruses were then tested on horses in Kentucky. "They vaccinated a group of animals and had a control group, and allowed them to mount their immune response. Then they challenged them with flu," she says, adding that the results were promising. "Basically the vaccinated animals didn't get sick."
With a turnaround time of a few weeks the reverse genetics route is quicker than more conventional approaches to vaccine development. This makes it an attractive option for keeping horse flu vaccines up to date as circulating viruses change over time, says Prof Cullinane.
"Equine influenza virus mutates readily and it's important that equine influenza vaccines are updated regularly with the current virus strains. Vaccine companies can be slow to invest in the lengthy procedures required to update equine influenza vaccines, but reverse genetics would accelerate the process as a master vaccine strain could be readily modified."