A new study conducted by University of Nebraska-Lincoln researchers found that the vaccines Nebraska hog farmers rely on to protect their animals from influenza can actually make lung disease more severe when the virus drifts to a new strain.
Another participating UNL researcher said a new approach could change that — and update to match emerging strains — within a month.
Hiep Vu, an associate professor of animal science at UNL, has developed a swine flu vaccine that uses lipid nanoparticles — tiny fat-like particles — to deliver DNA directly into muscle cells. Once inside, the animal's own cells produce a key flu protein, triggering an immune response without exposing the animal to live virus.
The approach is described in a paper accepted for publication in npj Vaccines, a journal dedicated to research and development on human and veterinary vaccines.
The problem with current commercial swine flu vaccines, Vu says, goes beyond just failing against mismatched strains. When vaccinated pigs encounter a flu strain that doesn't closely match the vaccine they received, the immune response can backfire which causes more severe lung damage than if the pig had never been vaccinated at all. Researchers call it vaccine-associated enhanced respiratory disease, or VAERD.
"If you perform the necropsy, you're going to see more severe lung lesion," Vu said. "Sometimes the animal will have higher fever compared to the non-vaccinated animal that are exposed to the same strain of virus."
In Vu's study, his DNA-based vaccine and a conventional protein-based vaccine used the exact same flu antigen — the same protein sequence from the same strain — but delivered it differently. When both groups of pigs were exposed to a mismatched strain, four of six pigs vaccinated with the conventional protein-based vaccine developed severe lung consolidation, more than three times the average seen in unvaccinated animals. Pigs vaccinated with the LNP-DNA vaccine showed little to no lung consolidation.
Vu says he doesn't fully understand why the delivery method makes such a difference, but hypothesizes it comes down to where the immune system encounters the antigen — outside the cell with a protein vaccine, or inside the cell when DNA is used. The exact mechanism remains an open research question.
The vaccine didn't stop pigs from shedding the virus nasally after exposure to a mismatched strain — meaning vaccinated animals could still transmit flu to others in the barn. Vu says that doesn't diminish the vaccine's value at the herd level. Vaccinated animals, he says, are generally more resistant to infection, need higher viral exposure to get sick, and shed less virus for shorter periods — creating a population-level effect even without complete protection.
Nebraska's hog industry includes roughly 3.6 million animals, according to the Nebraska Department of Agriculture.
One of the platform's key advantages is speed. Because the DNA-based approach uses only a single gene from the virus — not live virus — scientists can synthesize it chemically and work in standard biosafety facilities. Vu says that could allow a new strain-matched vaccine to be ready within a month of a new strain emerging, compared to the longer timeline required for conventional vaccine production.
That speed advantage matters especially for highly pathogenic strains like H5N1 avian influenza, which require more stringent biocontainment and can only be handled at a small number of facilities nationwide.
The research has already attracted commercial interest. Vu says a patent application has been filed through UNL's NUtech Ventures office, and the university is in discussions with companies about scaling up production and bringing costs down to a level viable for commercial farms.
Vu has also begun testing the platform in chickens, where early immune responses have been strong. The next step — challenging vaccinated birds with H5N1 — is pending access to a facility cleared for that work.
"If we have the vaccine working in multiple species, then we can respond faster because we don't have to develop anything from scratch again," Vu said.