A ground-breaking research project funded by Teagasc could result in dramatic improvements in the health of newborn calves. Teagasc research officer Dr Kieran Meade worked with leading TCD vaccinologist Prof Ed Lavelle to develop new strategies to improve vaccination design and formulation for cattle.
The scale of the problem being addressed is immense. More than 2 million calves are born in Ireland each year, and unfortunately approximately 7 per cent or 140,000 of these are lost to a variety of ailments including bacterial, viral and parasitic infections. Furthermore, respiratory and digestive diseases represent serious threats to the surviving cattle which can suffer from failure to thrive and other welfare issues as a result.
The issue up until now has centred on the relatively poor efficacy of vaccines in new calves, a problem shared with neonatal humans. Vaccines offer potential solutions to these diseases, but they are not straightforward to design, nor are they effective in all animals.
Calves pose a particular challenge as their immune systems are immature, and antibodies from their mothers can interfere with vaccine efficacy. In effect, the antibodies from their mothers respond to the vaccine before the calf’s immune system can. This greatly reduces the effectiveness of the vaccine.
Humans and mice
In addition, the current generation vaccines were often designed based on formulations used in humans and mice, and these do not work as well in livestock.
The breakthrough, made by Meade, Lavelle and PhD student Ciaran Harte, will facilitate the development of improved vaccines that target DNA sensors in immune system cells.
The science behind the research goes to the very basis of animal immune systems. Put simply, we have two immune systems: an innate and an adaptive system. The innate is the one we are born with while the adaptive is the one that develops and learns over time. Traditional vaccines have targeted the adaptive system by exposing it to an antigen. The immune system creates antibodies to the antigen and builds up resistance to the target disease.
Unfortunately, in newborn calves and children the adaptive immune system is very immature, and its learning capacity is hampered by the presence of antibodies from the mother. Even when those antibodies are not present the “memory” of the immune system cells at this stage is not very good or long lasting and the vaccines are therefore not very effective.
Innate immune system
Meade and his fellow researchers took a different approach and decided to target the innate immune system. “The innate immune system was not thought to have a memory up until now,” he explains. “Now we know it does. We are engaged in innate immune system programming. We are activating the cells in the innate immune system and training it to be fitter and faster in its response to diseases.”
Targeting the innate immune system requires a new way of formulating or delivering a vaccine. Meade points out that a vaccine is made up of two components, the antigen and an adjuvant. The role of the antigen is well known, but adjuvants are rarely heard of outside laboratories.
The adjuvant activates the immune response to drive long-lived memory. But the current generation of vaccines use a standard adjuvant which doesn’t work well in calves. The adjuvant employed in this instance is one that has been demonstrated to work well in calves and will activate innate immune cells.
“We can use it in two ways,” says Meade. “One way is to give the adjuvant to the animal first. That switches on the innate immune system. Then we hit it with the vaccine and it responds to that. The other way is to replace the existing adjuvant in the vaccine with this one so that it will target the innate immune system.”
This has many advantages. The main one being that the innate system will effectively bridge the gap left while the adaptive system matures. In addition, because of the nature of the innate system the immunity will last longer and fewer booster vaccines will be required.
Invention award
The team recently received the Bridge Network Consortium Teagasc Invention of the Year award for its work. The Bridge Network is a consortium comprising the technology transfer offices of Teagasc, UCC, Cork IT and IT Tralee.
According to Meade, the overall benefits of the new strategy will be reduced mortality in calves, a reduction in the occurrence of infectious diseases in cattle and lower the use of antibiotics in the longer term. The next step is demonstrating that it works. “We have done the in-vitro work in the lab and new want to proceed to in-vivo work out in the field,” says Meade. “We are applying to SFI and Teagasc and Enterprise Ireland for funding. We hope to begin work next year if we get funding.”