Scientists studying how fish, chickens, and pigs fight off infections are uncovering fundamental principles that could revolutionize vaccine design for humans. By comparing immune responses across different animal species, researchers are identifying which infection-fighting mechanisms have remained unchanged for hundreds of millions of years, suggesting they hold the key to more effective vaccines and better pandemic preparedness .

What Can Animal Immune Systems Teach Us About Fighting Viruses?

Comparative immunology, the study of how different animal species mount immune responses to infection, is revealing surprising universal truths about how all vertebrates defend themselves against pathogens. When a molecule or immune response works the same way in a fish, amphibian, reptile, bird, and mammal, it signals something crucial about survival. "If something doesn't change for 400 million years of evolution, it's really crucial," explained Professor Maria Forlenza, a newly appointed Professorial Group Leader in Immunology at The Roslin Institute. "It's the keystone in the middle of an arch. If you remove it, the whole castle collapses" .

Professor Maria Forlenza

"If something doesn't change for 400 million years of evolution, it's really crucial. It's the keystone in the middle of an arch. If you remove it, the whole castle collapses," explained Professor Maria Forlenza.

Professor Maria Forlenza, Professorial Group Leader in Immunology at The Roslin Institute

One of the most important discoveries emerging from this research involves how different species respond to viral infections. Across all vertebrates, viral infections trigger molecules called interferons very quickly and at high levels, but this response varies significantly between species. By matching interferon responses with the specific viruses affecting different animals, researchers are building a map of how immune systems evolved to handle different threats .

How Are Researchers Using This Knowledge to Develop Next-Generation Vaccines?

Understanding immune responses across species is already translating into practical vaccine development. Professor Forlenza has been involved in generating vaccines for multiple aquatic species and is now working on advanced vaccine technologies that could eventually benefit human health. Her research spans several generations of vaccine innovation, moving beyond traditional approaches to more sophisticated designs .

• DNA Vaccines: Forlenza helped develop a DNA vaccine against spring viraemia carp virus, a pathogen that affects farmed fish populations and demonstrates how genetic material can be used to trigger immune responses.
• Nucleic Acid-Based Vaccines: Current research focuses on making these vaccines safer and more effective by refining how genetic material is delivered to cells.
• Replicon-Based Vaccines: These third and fourth generation vaccines use self-replicating RNA that allows for significant replication within cells, offering potential advantages over traditional approaches for diseases like tilapia lake virus.

The work extends to Atlantic salmon and rainbow trout, expanding the range of species where these advanced vaccine technologies are being tested. Each species offers unique insights into how immune systems respond to different pathogens, providing a broader foundation for designing vaccines that work across multiple organisms .

Why Are Scientists Also Studying Immune Cells in Laboratory Conditions?

Beyond studying whole animals, researchers are developing laboratory-grown immune tissues called organoids to reduce the need for animal testing while maintaining scientific rigor. Organoids are miniature versions of organs grown in laboratory dishes, allowing scientists to study immune responses in controlled conditions. Forlenza is pioneering intestinal organoids for fish species, which could eventually allow researchers to study immune responses without conducting as many whole-animal experiments .

The intestinal tract is particularly important because it's a major site where the immune system encounters pathogens and learns to respond to threats. By growing carp, tilapia, and potentially Atlantic salmon organoids in the laboratory, researchers can observe how these tissues respond to infections and test new vaccines in a more controlled environment. Early results from this work are described as "very promising," suggesting this approach could soon become a standard tool in vaccine development .

The broader implications of comparative immunology extend beyond individual vaccine development. By identifying which immune mechanisms have been preserved across hundreds of millions of years of evolution, scientists can focus research efforts on the most fundamental and likely effective targets. This approach could accelerate vaccine development for emerging infectious diseases and improve our ability to respond to future pandemics by revealing the universal principles that govern how all vertebrate immune systems work .