It’s a colossal investment of time, money, and passion that brings a healthy foal into the world, and most breeders take every precaution to maximise the chance that foal can grow out and fulfill their potential on the track. Vaccination regimes play an important role in this process, but there are some diseases that we cannot yet protect against.
The AgriFutures Thoroughbred Horses Program and researchers from the University of Queensland are working to change that for rattles.
A difficult disease to prevent
Rattles is the colloquial name given to the symptoms of pneumonia caused by the Rhodococcus equi bacteria, and it can ravage a young foal’s respiratory system in a very short period of time. Foals under five months of age are most at risk, especially as immunity provided by the mare begins to wane.
Foals who become very sick can require intensive care, up to and including breathing support, being in an air conditioned stable, and nebulised antibiotics, all of which come at great expense to the breeder - and some will be plagued with lung problems for the rest of their lives.
What makes it so difficult to combat - and why in particular a vaccine is so pressing to develop - is where the bacteria can live.
Tim Mahoney | Image courtesy of University of Queensland
“One of the main problems is that the pathogen is almost ubiquitous in the environment,” said Professor Tim Mahoney, Professor and Director of the Centre for Animal Science at the University Of Queensland. “It can live in the soil, which makes it very difficult to control exposure, particularly when it's dry and dusty. That makes it difficult to protect the foals using our normal biosecurity measures, like planning animal movements, moving feeders, and disinfecting areas like the crush and the stables.
“(Rhodococcus equi) can live in the soil, which makes it very difficult to control exposure, particularly when it's dry and dusty.” - Tim Mahoney
“Because it's so difficult to control exposure, foals are at a risk of being exposed to it all of the time. On top of that, it's also a difficult organism to treat. We would do that with strong antibiotics and antimicrobials, and we would want to get to the affected animals as quickly as possible to try to reduce severe effects. But there's still going to be a number of foals that succumb to it.”
Preventative care is always cheaper than the cure, and Mahoney can see another benefit for minimising the amount of sick foals through a vaccination program.
“Generally, we are trying to move away from heavy use of antibiotics and antimicrobials in animals,” he said. “Doing so has the potential risk of contributing to growing resistance to different antibiotics, so the less we have to use them, the better.”
The makings of a vaccine
The origins of Mahoney’s team’s current push to make a vaccine for rattles is, as Mahoney puts it, “like a COVID vaccine story”.
“A student at Charles Sturt University called Carla Giles started the work around 10 years ago,” Mahoney said. “She was working on a vaccine that was constructed similar to AstraZeneca, which is a viral vector vaccine. She made the original vaccine construct using what we call a replication deficient virus, which is from the same family as what was used in AstraZeneca.”
“(Carla Giles) was working on a (rattles) vaccine that was constructed similar to AstraZeneca, which is a viral vector vaccine.” - Tim Mahoney
Viral vector vaccines use a benign or severely weakened form of a virus as a carrier of DNA from the target pathogen. When injected into an animal - or human - the animal’s cells are able to take the genetic instructions and form an immune response to them, without the animal getting infected. An adenovirus - the family of viruses that cause the common cold - was selected as the most suitable vector.
“Once you use the viral vector vaccine to immunise an animal, the virus and what it carries is not able to replicate in the animal,” said Mahoney. “It just directs the production of the vaccine components and stimulates immune responses from the body.
Carla Giles | Image courtesy of ResearchGate
“Carla did some animal studies using mice to show that the vaccine was able to produce the antigen, and then she also did a challenge study in mice.”
A challenge study involves injecting the pathogen into a subject in order to how well it colonises the subject, or how well the medication or vaccine can combat the pathogen.
“It's not a true model for rattles because the bacteria doesn't actually colonise mice, but she was able to show that the level of true colonisation was actually reduced in the vaccinated ones, suggesting that the vaccine could be protective in horses,” Mahoney said.
“(Carla) was able to show that the level of true colonisation was actually reduced in the vaccinated (mice), suggesting that the vaccine could be protective in horses.” - Tim Mahoney
The project was then able to make the next crucial step with the University of Queensland, progressing to horse trials with funding from AgriFutures.
“We applied for the funding to see if we could test the vaccine in foals, and in the process, we discovered something that concerned us,” said Mahoney. “We were able to produce the vaccine in the lab, but we weren't able to produce it in large quantities. That had us worried that, if we did the whole study and found it was effective, we would not be able to produce it on a commercial scale.”
Fortunately, the acceleration in vaccine technology brought about by the COVID-19 pandemic had an answer that could offer a way forward.
The animal as the vector
“We knew there was no future for the original vaccine if we couldn’t produce it on a mass scale,” Mahoney said. “Those discussions were happening around the same time as the pandemic, and since then, there's been so much investment and development of mRNA usage in vaccines. We looked at what else was available to us and we thought, why don't we try and bring in the most up-to-date technology we possibly can to see if we can address this disease?”
“We looked at what else was available to us and we thought, why don't we try and bring in the most up-to-date technology we possibly can to see if we can address this disease?” - Tim Mahoney
Unlike virus vector vaccines, a mRNA vaccine is far more simple in what it constitutes outside of the body. Messenger RNA carry “blueprints” to produce the proteins and enzymes of a pathogen, and usually take a very small part of the pathogen - for instance, the mRNA-based COVID vaccines use the mRNA for the “spike protein” that is a small but necessary component of the virus.
The vaccine takes messenger RNA from a pathogen, as opposed to a much larger part of the pathogen as in the viral vector vaccine, and puts that directly into the cells of an animal, who recognise the intruder as a foreign protein and mount an attack against it.
“Because the animal cells themselves are actually making the active part of the vaccine, it is very efficient for us,” Mahoney said. There is no risk of being exposed to the pathogen itself with an mRNA vaccine as it constitutes only a very small part of the pathogen.
“We only have to produce the basic components of the vaccine. Usually when we're doing vaccine development, actually producing the antigens or the protein components that we might inject into animals is usually a very laborious and quite expensive process. So using mRNA enables us to shortcut that process and produce vaccines that are likely to be easier to produce, and therefore they should be cheaper to the end users.”
“Using mRNA enables us to shortcut that process and produce vaccines that are likely to be easier to produce, and therefore they should be cheaper to the end users.” - Tim Mahoney
In addition to the process itself being quicker and more efficient, the laboratory technology required to produce the vaccine on a large scale is much more simplistic, and Mahoney is hopeful that, if the vaccine makes it to the commercialisation stage, costs can be kept very low for breeders.
Preparing to trial
The University of Queensland team is in the process of pivoting fully to the mRNA vaccine idea and is preparing to hopefully test the vaccine on a select foal population during the 2026 breeding season.
“Obviously we will need to get all of the required approvals in place for animal experiments, such as approval from the animal ethics committee, but we are hopeful we will be in the position to start the trial this year,” Mahoney said. As in trials for human drugs, there is a need to work out if the vaccine will cause any adverse reactions, as well as if it will work in horses.
“We have a laboratory at University of Queensland that is capable of making the vaccines and we are working on sourcing foals for the trial. We will need to screen them for immune response and maternal antibodies, and ensure that we select mare-foal pairs who don’t respond to the bacteria first, as we will be able to more easily detect a specific response to the vaccine.
“The aim is that early next year, we will be analysing samples collected during the trial and seeing how well they have responded to the vaccine.”
“The aim is that early next year, we will be analysing samples collected during the trial.” - Tim Mahoney
University of Queensland mRNA Vaccine Laboratory | Image courtesy of University of Queensland
The trial will test two dose strategies in foals, assessing safety, antibody production, and cellular immunity of each, with the intention of releasing an information dossier for the industry at the conclusion of the study. From there - all being well - a commercial vaccine to protect against one of the Thoroughbred industry’s most threatening diseases could be on the horizon.
“We are grateful for AgriFutures’ continued support of the project,” Mahoney said. “We are excited about the progress we expect to make this year, and what that could ultimately mean for breeders and the long-term health of foals across the industry.”
