Swine vaccine management requires continuous attention
The COVID-19 pandemic holds important lessons for swine health professionals not only about the nature of viruses, but also the importance of vaccines and the need to manage them carefully, said Lars Erik Larsen, professor of veterinary virology at the University of Copenhagen, Denmark.
“It’s basic biology, but the coronavirus has revealed viral evolution and mutations and why it’s so difficult to develop effective vaccines,” Larsen said during a session on vaccine safety and risks at the European Symposium of Porcine Health Management 2020+1 virtual meeting. “We are chasing a moving target when we talk about viruses and vaccines.”
Of course, the COVID-19 challenge has also revealed how vaccine development technologies are changing. “Today, vaccines are often generated by genetic manipulation in the laboratory,” he noted.
Still, there are many swine vaccines, including those for porcine parvovirus, porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome (PRRS), that are created from inactivated and modified-live viruses (MLV). Although MLV vaccines are generally safe and critical to the control of these important swine diseases, their ability to recombine with other viruses and form new, potentially virulent strains highlights the need to manage them with care.
RNA viruses — including coronaviruses, PRRS viruses and swine influenza — are a particular challenge as they have developed mechanisms that allow them to rapidly adapt and respond to changing ecological conditions. Point mutations are a common feature in RNA viruses, occurring over multiple selections and transmissions and allowing the “most fit virus” to infect the next host, Larsen said. This is a rather slow process.
However, viruses can more quickly change through two other methods:
1) Recombination occurs when viruses of two different parent strains coinfect the same host cell and mix to create a strain that’s different than either of the parent strains.
2) Reassortment is another form of genetic exchange that can occur in segmented viruses, such as influenza, when their genome splits into multiple segments. Viruses mix within a segment, creating a new virus with completely different phenotypes; it may be more virulent and infect hosts that the original viruses couldn’t infect.
For a perspective of how fast viruses evolve, Larsen noted that if the same timeline were applied to human evolution, the entire transformation would have taken just 38 years.
Swine influenza virus is known for its ability to undergo antigenic shift and drift, with some examples of vaccines assisting the viral evolution. There’s also much discussion about PCV2 genotypes that shift in dominance in a region or country, raising questions about the long-term impact on vaccine effectiveness.
MLV vaccine challenges
In recent years, there have been more reports of recombination between PRRS field viruses and PRRS MLV vaccine strains. “Sometimes these mutations are very isolated,” Larsen said. But they can escape and spread to other herds.
“These [viral mutations] are important when we talk about the risks of MLV vaccines, because MLV vaccines have been attenuated by repeated passage in vitro to decrease the capability to induce clinical disease in the vaccinated host,” he added. “These mutations can converge with the attenuated strain into a more pathogenic type.”
Also, with MLV vaccines there’s a risk of the virus transmitting to unvaccinated animals within the herd or to other herds, allowing the virus to replicate and undergo repeated pig-to-pig passages. This allows repeated “bottle-neck” selections that assist virus recombination.
It’s critical for swine practitioners and farmers to comply with the manufacturer’s instructions for all MLV vaccines, Larsen said. His advice: “Vaccinate all animals in a given epidemiological unit at the same time and do not mix vaccinated and unvaccinated animals until after the end of the shedding period.”
PRRS ‘almost impossible to control’ without MLV vaccines
Although there may be safety challenges with MLV vaccines that deserve attention, the vaccines still play an important role in controlling swine diseases. “PRRS would be almost impossible to control if we didn’t have MLV vaccines,” Larsen said, adding that farmers and swine veterinarians need to be aware of concerns when using them.
He told ESPHM participants to expect increased attention to MLV vaccines from the European Medical Agency, noting that some have called for tighter regulations around their use.
However, Larsen said he’d like to see more flexible regulations to allow faster viral strain updates to vaccines. “It is so costly for companies to update their strains,” he stressed. “We are addressing moving targets with RNA and DNA viruses; I would love to have a more flexible system so companies are allowed faster development.”
One way to mitigate the negatives associated with MLV vaccines is for companies to avoid using the “hottest” field strains as vaccine strain seeds, Larsen suggested.
He also recommended that farmers and veterinarians initiate a “flushing period” when making MLV vaccine changes. “This is not easy to do, but the point is to get the first strain out of the [animals’] system before you bring in a new one,” he explained.
More research is needed on viruses and their potential interplay with vaccines, Larsen said. One area of particular interest is the impact of repeated vaccinations, particularly when MLV vaccines are involved.
“We put a lot of vaccines into the pig,” he said. “We often vaccinate 3 to 4 times a year with influenza, but also PRRS. Does repeated exposure with the same strain change the efficiency of the antibody response?”
For older sows, that means they may be exposed to identical antigens as much as 20 to 25 times during their life-span, he added.
Furthermore, “we need to consider whether there’s an order to give shots, and thereby produce better immunity,” Larsen said.
Discussions about non-specific effects of vaccines, which can be beneficial or detrimental, are gaining ground on the human side and he would like to see this investigated in more detail in swine.
In conclusion, Larsen said, “We have to keep our eye on all of these viruses — especially the RNA viruses, but also the DNA viruses that are mutating at a similar rate. So, we cannot just sit back and enjoy vaccines, we have to follow the individual cases.”
Posted on June 23, 2021