Porcine reproductive and respiratory syndrome virus (PRRSV) can have a huge economic impact on a hog operation.
So finding better vaccines against the disease would be a huge boost to the hog sector.
That’s why a long-term, international collaboration between researchers at the University of Manitoba and the Leiden University Medical Centre in the Netherlands uncovering vital information about PRRSV is such good news for the sector.
For those unfamiliar with PRRSV, the pathogen causes severe disease in pigs, leading to significant economic losses for pork producers across the globe.
“PRRSV is a virus that causes respiratory disease in young pigs, but it is most known for its reproductive impairment or failure, whereby still births and mummified fetuses are frequently seen in sows, sometimes causing very significant losses on pig farms,” Marjolein Kikkert, Associate Professor of Virology at Leiden University Medical Centre told Prairie Hog Country. “It is the most impactful viral disease in pigs causing an estimated 664 million dollars in annual losses for the U.S. pig industry alone. This figure is probably much higher in the Asian pig industry, and the disease plays a role in pig industries worldwide.”
The aim of the project was to improve vaccines for the disease, which proved very difficult.
Kikkert and collaborator Brian Mark, Dean of the Faculty of Science at the University of Manitoba, looked at targeting a type of protein called a protease. PRRSV uses these proteins to suppress a host’s immune system, causing severe illness. By changing the structure, researchers can design altered viruses upon which to base new vaccines.
With the help of the Canadian Light Source (CLS) at the University of Saskatchewan (USask), Mark and Kikkert were able to visualize the unique structure of the PRRSV protease. What they learned in their study is valuable for developing new vaccines against PRRSV and also helps inform development of vaccines against emerging human viruses.
“This kind of protein in viruses was our focus and we found that small changes engineered on these viral proteases may change the character of a viral vaccine — those vaccines that contain this protein — so that the vaccine may be safer and works better,” said Kikkert. “The principle in the end turns out to work very well on some viruses (MERS-CoV), but unfortunately not on others (PRRSV and SARS-CoV-2).
“This is what we have now learned.”
The team has conducted similar research on coronaviruses — which also use proteases to suppress human and animal immune systems — and has successfully designed new vaccines.
“The trick and hypothesis we had for improving the PRRSV vaccine didn’t quite work,” said Kikkert in a release. “However, we did learn a lot about how these viruses work. And it may certainly be a basis for further work into possibilities for improving vaccines against these viruses and coronaviruses.”
The team’s findings also unlock new doors to understanding how viruses like PRRSV use proteins to replicate, making this a significant academic discovery.
Ultimately, it was the effort of two universities on different continents which Kikkert was happiest about.
“I think the beauty of this whole story is in how collaborations like these can gain basic scientific knowledge that is applicable in unexpected ways to solve problems in society,” she noted. “This is a clear plea for fundamental scientific research which is based primarily on curiosity, and in many cases in the end is the only way to solve problems in innovative ways.”
As for the specific project Kikkert explained, “we entered into the work on PRRSV around end of 2012, beginning 2013 if I am correct. So it took us a decade to finally publish the PRRSV work. The first paper Brian (Mark) and I published as collaborators is from 2013 on EAV, and we published a total of nine scientific papers together between 2013 and today, including this recent one on PRRSV.”
Interestingly, the university where Kikkert comes from is not heavily into swine research.
“No, we are an academic hospital (Leiden University Medical Center) and usually do not work on animal diseases,” she said. ”However, the university hospital has been doing research on human coronaviruses for decades, but since these are sometimes difficult to work on — due to their genetic structure: they have relatively large genomes — and dangerous for humans so dealing with safety restrictions (having to work in BSL-3 laboratories), we were sometimes using animal-infecting arteriviruses, like EAV; equine arteritis virus, another virus we have worked on and PRRSV as more workable models for our research. These viruses resemble the coronaviruses quite much, but have much shorter genomes and are less dangerous to work with since they do not infect humans. Since some of them, particularly EAV (infecting horses) and PRRSV (infecting pigs) are actually important animal pathogens, our results sometimes drew interest from people from the veterinary world.

“Now, coincidentally, there was a PhD student from the LUMC Virology group, who after his graduation got a job at an animal health company. He saw me present some of our work on EAV one day (around 2012) at a conference and then approached me with the idea that our specific scientific knowledge on proteases from corona and arteriviruses could maybe help improve the efficacy of vaccines against PRRSV. These vaccines have never worked optimally, so the room for improvement may come from our scientific insights, and we then entered into a research contract with them, which included Brian’s group as well. The crystal structures of the viral proteases we were looking at were thought to be essential for the solutions we were looking for, and this is why Brian was involved from the beginning.”
And, collaboration is a good way to expand research.
“There are many, for example I had a chance of visiting Manitoba, and saw how Brian lives, meet his group, give a seminar etc, and reciprocally Brian visited Leiden.
“One of my PhD students spent research time at Manitoba, and one of Brian’s group members came to Leiden for a few weeks to gain some experience here.
“I think it is always beneficial for researchers to see how things work in different places in the world and learn from other people’s skills and expertise. Science is a global thing!
“Writing manuscripts for papers together was very efficient given the time difference: when we sent a version to Canada we would have it back the next morning, since they could work on it while we were sleeping.
“But a very important aspect of this interaction was the complementary expertise the two groups have: in Leiden we are virologists and Brian is a crystallographer, and in the research we were doing those two skills were essential to solve the scientific questions at hand. On top of that we both had interests in viral proteases, a particular kind of protein, and that combination is not so easy to find between two groups.
“But most prominently, and what I think made it such a longstanding and productive collaboration was the super-pleasant way me and my group members worked together with Brian and his people. This just went so smoothly due to a combination of our characters, our standards and our views, which aligned very very well. This is not trivial in collaborations and I have not experienced a better match with any other collaborator in my career.
“And I think this is the main reason why it lasted this long. So in that sense the distance is not a particular advantage, but if the match is good it is so worth it!”
So what comes next?
“Good question. Of course there are plenty more questions left on the subject, but whether these will point to more possible solutions for vaccines I don’t know,” offered Kikkert.
“However, investigating viruses and how they operate and interact with their host cells will never stop intriguing me/us!”
So at least for now a new PRRSV vaccine which could help producers is not close based on the research so far.
“The trick we had in mind does not seem to work for PRRSV. We don’t exactly understand why not, so by further investigating the interaction of PRRSV with the host cell we may one day be able to improve vaccines and other antiviral remedies against PRRSV, but this will take more work,” said Kikkert.
“Indeed, our collaboration over the years has been fantastic. PRRSV has certainly been the most complex virus we worked on together, but I hope our recent work provides one more piece of the puzzle toward an improved PRRSV vaccine. Not quite there yet as you say,” echoed Mark. •
— By Calvin Daniels