RFLP 1-7-4, variant 1C.5 (aka L1C-4-4), or 1C.5.32 – these are some of the infamous PRRSV-2 viruses that have caused massive production losses over the past decade. Regardless of how people named or classified them, one thing these epidemic waves had in common was that they were caused by genetic variants that were novel at the time, and vaccination, especially widely used modified-live virus commercial vaccines, failed to mitigate their spread. Many viruses are in an arms-race with host immunity, evolving to evade host immune mechanisms. The less-than-perfect available immunization strategies combined with the expanding genetic diversity seen for PRRSV-2 raises the question:
Does the use of MLV vaccines play a role in shaping wild-type PRRSV-2 evolution, potentially driving the emergence of new variants?
A newly published paper from the University of Minnesota1 attempted to answer that question in a controlled experimental setting to compare the evolution of PRRSV-2 through pig-to-pig infection chains under different MLV vaccination conditions.
Experimental design and analysis
The study was designed to mimic the natural process of PRRSV-2 evolving over time as it transmits through successive batches of pigs with different immune backgrounds. Weaned pigs were divided into two vaccinated groups (each receiving a different commercial MLV vaccine) and one unvaccinated, naïve group.
Each group included about seven pigs, which were challenged at 64 days post-vaccination with a PRRSV-2 sub-lineage 1A (L1A) virus. Serum samples were collected for 14 days post-challenge, and these samples were used to infect the next group of seven pigs in the same treatment. This process was repeated for six batches of pigs, involving a total of 126 pigs over roughly 84 days.
In total, 110 PRRSV-2 genomes were successfully sequenced using third-generation deep sequencing technology. Researchers analyzed how far the viruses diverged from the original challenge virus (ChV) at the genome level and assessed viral diversity at the quasispecies level—the collection of closely related mutated viruses within each pig—to understand how evolutionary patterns differed among treatment groups at the finest scale.
Key findings
- Greater genetic divergence was observed under vaccine pressure: Viruses from vaccinated pigs evolved more than twice as much from the original ChV (0.3–0.4% mean genetic distance) compared to viruses from non-immunized pigs (0.15%).
- Distinct viral populations emerged in vaccinated groups: Vaccine pressure led to a rapid shift in viral quasispecies composition, producing viral populations that were genetically different from the ChV. Some dominant mutants in vaccinated pigs had not been present in the initial virus population.
- Lower viral loads in vaccinated pigs: Despite greater genetic divergence, vaccinated pigs consistently had higher Ct values, indicating lower viral load compared to unvaccinated pigs.
What can we learn from this?
This study provides strong experimental evidence that vaccination influences PRRSV-2 evolution, driving genetic changes that result in viral populations distinct from the original challenge virus. Vaccinated animals harbored viruses that were more genetically diverse and distinct from the parent virus. However, even though viruses diversified more in vaccinated pigs, they were present in much lower quantities, so their transmission potential in vaccinated pigs is unclear under field conditions.
That said, the findings also indicate that novel variant emergence driven by vaccine pressure is possible, meaning that viruses can adapt to immune pressure and take on new genetic forms over time. This highlights the importance of continuous monitoring for changes in circulating PRRSV populations, even on well-vaccinated farms.
However, simply not using MLV is often not the solution, as MLV remains amongst the best available options to reduce clinical impacts. But judicious vaccine use, along with strong farm management practices—such as strict biosecurity and routine PRRS monitoring—could be the key to both controlling disease and preventing the emergence of unprecedented viral variants that may arise from the continuous evolution of persisting viruses in a farm environment.
Conclusion
MLV vaccines effectively reduce PRRSV-2 viral loads but accelerate genetic evolution, potentially creating new variants. Strategic vaccine application combined with robust biosecurity and ongoing viral surveillance offers the best approach for disease management. While vaccination remains essential, comprehensive farm practices are crucial to prevent emergence of novel strains that could evade current control measures.
1 Citation: Nakarin Pamornchainavakul, Igor A D Paploski, Dennis N Makau, Julia Baker, Jing Huang, Clarissa P Ferreira, Cesar A Corzo, Albert Rovira, Maxim C J Cheeran, Samantha Lycett, Andrea Doeschl-Wilson, Declan C Schroeder, Kimberly VanderWaal, Experimental evidence of vaccine-driven evolution of PRRSV-2, Virus Evolution, 2025;, veaf056, https://doi.org/10.1093/ve/veaf056
This article was written by Nakarin Pamornchainavakul and Kimberly VanderWaal of the University of Minnesota for the National Hog Farmer.