Researchers from The Pirbright Institute in the U.K. collaborated with the University of Oxford and the U.S. National Institutes of Health to show that S-FLU — a universal flu vaccine candidate — induces different immune responses in pigs compared to ferrets, raising the possibility that the ferrets may not give the whole picture and that pigs may more faithfully represent human influenza disease.

According to the announcement from Pirbright, the team also identified a new type of T-cell in pigs that is able to rapidly help fight respiratory infections.

There are many strains of influenza, each of which has a different outer coat and is able to rapidly mutate, fooling the immune system and rendering the antibodies produced to one particular strain ineffective against other strains, Pirbright explained. This presents a major obstacle when developing vaccines that act against multiple flu stains, as conventionally vaccines trigger antibody responses that are specific to the strain contained in the vaccine.

The S-FLU aerosol vaccine, developed by Alain Townsend at the University of Oxford in the U.K., is a weakened strain of flu virus designed to trigger a response from T-cells that can react to multiple strains of flu, Pirbright noted. This differs from conventional flu vaccines that activate antibodies that respond only to the strain contained in the vaccine.

The research, published in the Journal of Immunology, demonstrated that, when administered to pigs, S-FLU was able to activate newly identified T-cells — called tissue-resident memory T-cells — against a flu virus of a different strain. Disease severity was also reduced, but the amount of virus remained the same, Pirbright said.

On the other hand, when S-FLU was administered to ferrets, viral replication was reduced, as was the amount of virus that was transmitted to other animals, Pirbright noted.

This striking difference in response to the exact same vaccine raises the question whether the ferret -- an animal model that is considered gold standard for influenza research -- provides results that are transferable to people, Pirbright said, noting that pigs provide a model that is more similar in size, naturally infected by influenza viruses and with a very similar respiratory system to humans.

The group’s discovery of tissue-resident memory T-cell activation in pigs also brings them closer to understanding how influenza is combated in the lungs. Dr. Elma Tchilian, head of the mucosal immunology group at Pirbright, said, “The identification of these T-cells will allow us to establish how best to induce and maintain them in the lung and help us make more effective vaccines against influenza and other respiratory diseases in both livestock and humans.”

The results also show that targeting the lower respiratory tract with aerosol vaccination in pigs may be more effective than other routes of immunization in preventing severe disease, which provides promising evidence that this method of vaccination could be successful in people as well, Pirbright added.

This work was supported by grants from the Bill & Melinda Gates Foundation, the U.K.'s Biotechnology & Biological Sciences Research Council and the Townsend-Jeantet Prize Charitable Trust.