Research led by scientists at The Pirbright Institute has highlighted the role played by pigs as a key natural host and important preclinical model for influenza.
The study, published today in Discovery Immunology, shows that pigs can generate antibody responses similar to those seen in humans, including antibodies that recognise vaccine-adaptive mutations and conserved viral stem regions.
Led by Prof. Elma Tchilian, Head of Mucosal Immunology at Pirbright, and carried out in collaboration with Dr Pramila Rijal and Prof. Alain Townsend from the University of Oxford, the research addresses a longstanding gap in comparative immunology: the absence of well-defined influenza-specific mAbs derived from pigs.
Essential tools for understanding viral evolution, monoclonal anitbodies (mAbs) guide therapeutic development and inform vaccine design. While influenza mAb development in humans has progressed rapidly, equivalent reagents from pigs have been lacking, despite pigs being a major intermediate host and physiologically relevant large-animal model.
Using infection and sequential immunisation strategies, the researchers generated and characterised porcine mAbs directed against H3, H5, and H7 influenza haemagglutinins (HA). These antibodies revealed key parallels between porcine and human immune recognition.
One notable finding relates to reduced vaccine effectiveness during the 2016 to 2018 influenza seasons. Egg-adaptive mutations in H3N2 vaccine strains, particularly in antigenic site B of the HA head, were implicated in diminished protection.
In this study, pigs inoculated with an egg-derived H3N2 virus generated an antibody (H3-57) that specifically recognised the egg-adapted mutation L194P. Importantly, this mirrors human antibody responses that preferentially bind egg-adapted variants rather than circulating wild-type strains.
The observation shows pigs can faithfully model how vaccine production methods influence immune responses in humans.
Beyond strain-specific responses, the researchers also identified cross-reactive antibodies targeting the conserved HA stem region. The ability to generate porcine stem-reactive mAbs has important implications for improved vaccine design, therapeutic antibody discovery in a physiologically relevant large-animal model, enhanced pandemic preparedness through better modelling of immune responses, and comparative immunology insights into cross-species antibody recognition.
While monoclonal antibodies have been developed against several major swine pathogens, this work represents the first comprehensive generation of porcine influenza mAbs directed against H3, H5, and H7 haemagglutinins.
Prof.Tchilian said:
“These developments in porcine monoclonal antibody research advance our understanding of similarities and unique features of antibody responses across species. By understanding how pigs recognise conserved and variable epitopes that mirror human immune recognition patterns, our work provides important translational insights that can aid the development of novel therapeutics.”