Researchers study swine immunity to unlock better flu vaccines
By Cynthia Williford Bean
Since September 2025, more than 24 million Americans have come down with the flu. Most of those cases were caused by a highly mutated version of influenza A, the H3N2 K subclade, that showed up last summer, long after the strains of flu used to formulate this year’s flu shot were chosen.
Years like this drive researchers like Dr. Constantinos Kyriakis to study and find ways to improve influenza vaccines, which have largely followed the same development process for decades. Step one: evaluate current strains to predict which ones will be dominant next flu season. Step two: use those to create a vaccine that will train the body to target and fight those strains.
Year-to-year, the effectiveness of flu vaccines averages between 19-60%. A highly adaptable virus, influenza is known to find ways around established immunity in its hosts, creating an ever-moving target for vaccine developers.
“While current vaccines are generally effective in preventing severe disease, there’s room for improvement when it comes to short- and long-term efficacy,” said Kyriakis, an associate professor in the College of Veterinary Medicine’s Department of Pathobiology.
Using swine as a model
A swine veterinarian and influenza virologist, Kyriakis possesses nearly 22 years of influenza research. He and his team, including Postdoctoral Research Fellow Dr. Fletcher North, are working with pigs to better understand immune responses to influenza viruses.
“There are several factors that make pigs a great model for influenza research,” North said. “They are natural hosts of influenza, and they exhibit similar disease symptoms like coughing, wheezing, fever — all the things you would think of as symptoms in people. Pigs and humans also have similar respiratory anatomy and immune responses, and they share very similar influenza virus strains.”
By studying pigs, North and Kyriakis hope to unlock keys to a more effective vaccine for humans that doesn’t solely rely on predicting which strains will stick around till next season.
The impact of immune responses
“One of the theories on why seasonal vaccination for flu doesn’t perform as well as we would like it to is the presence of pre-existing immunity,” North said.
That includes a phenomenon called original antigenic sin, or immune imprinting.
“The premise of this theory is, depending on the initial virus strain that a child encounters, that immune system will always be better prepared for that type of virus,” Kyriakis explained.
North evaluated immune imprinting in several groups of swine in his doctoral work, which was funded by the National Institutes of Health (NIH) Centers of Excellence for Influenza Research and Surveillance (CEIRS), through the Emory-UGA CEIRS Center.
He found that imprinting depended not only on the subtype of virus individuals are infected with but also on the severity of the initial infection. Imprinting was more pronounced in animals that were symptomatic compared to infected animals that didn’t show symptoms. Additionally, vaccination before infection seemed to balance responses to future infections.
North and Kyriakis also assessed the effectiveness of Centi-Flu — a broadly protective or universal influenza vaccine development by Centivax, a biotech company from California — in both pigs who had been exposed to the virus and those who had no previous exposure. North found that the pigs previously vaccinated and/or infected with influenza had significantly higher antibody responses to a broad range of viruses when vaccinated with Centi-Flu compared to influenza-naive animals.
This was a key finding. Since most humans have a degree of pre-existing immunity through seasonal vaccination and previous infections, the hypothesis is that a universal vaccine could help boost responses and offer better protection than the current seasonal influenza vaccines.
“Pre-existing immunity can have profound effects on how an individual responds to future exposures including vaccination,” North said. “This makes it an important avenue of research when trying to improve upon current vaccines.”
A way forward
Researchers commonly use ferrets with no prior exposure to influenza to identify virus strains and evaluate the effectiveness of each year’s flu vaccine. Since immune imprinting can impact the effectiveness of vaccines, North’s work suggests that testing flu vaccines in swine — which have similar immune imprinting patterns to humans — could provide a more comprehensive understanding of how vaccines will affect people with pre-existing immunity.
While his study was a “step in the right direction,” North noted there’s much more work to be done. He is now following up his previous work, studying how pre-existing immunity impacts the evolution of influenza viruses by analyzing their genome.
Kyriakis compared his and other research underway across the globe to a gear in the intricate Swiss watch of vaccine improvement — it’s all needed to chart a path forward.