Influenza viruses are a major threat to health in livestock and humans. Influenza viruses are spread through contact, large respiratory droplets and aerosols, however factors affecting these modes of transmission are poorly understood.
Economic losses due to swine influenza are significant, ranking among the top three major health challenges in the swine industry. Importantly swine influenza (SI) is a zoonotic threat and swine viruses are implicated in human influenza pandemics.
The goal of our research is to develop better prevention strategies for respiratory pathogens in animals and humans. To do this we study the pig as a large animal natural host model of immunity to influenza, in which the effects of pre-exposure to diverse influenza strains can be investigated.
- To improve immunisation strategies for inducing long-lived high affinity broadly neutralising B cell memory in pigs.
- To test prophylactic and therapeutic monoclonal antibodies and to uncover mechanisms underlying their protective efficacy.
- To determine the importance of local T cell immunity, including lung tissue resident memory cells, in respiratory infections and develop improved strategies to induce local immunity.
- To understand transmission dynamics of swine influenza, determine correlates of transmission and means of preventing transmission.
We have now developed many tools to study immunity in pigs, including cell transfer, tetramers, the use of selective immunosuppressive agents and means of enumerating tissue resident memory cells. We have shown that aerosol delivery of a candidate vaccine is highly efficient in inducing heterosubtypic protection against swine influenza and that vaccine induced protection differs in ferrets and pigs. We have begun to investigate antibody (Ab) function and specificity in the pig influenza model and have successfully demonstrated its value in testing the protective efficacy of human mAbs. We are generating pig influenza specific mAbs which will create novel delivery platforms for animal health.
These tools and experience make pigs an invaluable model to study immunity against respiratory infections for improvement of animal and human health. Understanding how best to induce and maintain lung tissue resident memory cells will enable us to make more efficient vaccines. Establishing the pig as a robust model to test mAbs and vaccines would allow us to scale up novel control strategies from small to large animals prior to human use. The generation of broadly neutralising pig influenza specific mAbs will provide alternatives to vaccines and therapeutics. Determining the viral and host factors related to transmission will enable better control measures to prevent disease, to be developed and applied.