Researchers at The Pirbright Institute have developed a robust large-animal model to show how the mucosal delivery of monoclonal antibodies (mAbs) and other immunoprophylactic agents can help prevent transmission of respiratory pathogens.
Supported by funding from the Gates Foundation, the findings establish the pig as a powerful and practical model for studying prevention of respiratory infections, addressing a critical gap in preclinical testing.
Writing in npj Vaccines, the Pirbright team explain how they used pigs, a natural host for influenza viruses, to create an advanced experimental platform to study how mAbs can be delivered directly to mucosal surfaces such as the lungs and nasal passages to block viral transmission. mAbs are lab-made proteins, designed to target and attach to specific proteins on the surface of cells, such as cancer cells or pathogens.
Mucosal delivery through inhalation, nasal sprays, or topical application allows antibodies to target infection sites directly. The approach may enable lower effective doses, faster immune responses and improved patient comfort compared to systemic (injected) treatments. The method could be used to treat respiratory illnesses like influenza, coronaviruses or respiratory syncytial virus infections,
The level of refinement and reproducibility achieved makes the pig model a valuable resource for the wider research community, offering an ethical and physiologically relevant alternative to ferret and non-human primate models.
Key findings:
- Aerosol and intravenous delivery of mAbs proved most effective for preventing influenza transmission.
- Intranasal delivery offered partial protection, preventing infection in some but not all contact animals.
- The direct challenge model provided comparable results to the more resource-intensive contact challenge, allowing for more efficient experimental design.
The findings provide a framework for testing immunoprophylactic interventions aimed at reducing respiratory pathogen transmission in humans.
Professor Elma Tchilian, Head of the Mucosal Immunology Group at The Pirbright Institute, said: “This work is particularly timely, as no monoclonal antibodies are currently approved for intranasal or pulmonary administration, despite increasing recognition of the importance of mucosal immunity in controlling respiratory diseases. Our study provides a comprehensive analysis of delivery routes and dosing strategies and establishes a reproducible platform to support future immunoprophylactic research.”
The researchers developed and optimized both direct and contact challenge models to assess mucosal delivery of antibodies, refining parameters such as virus dose, co-housing conditions, and duration of exposure. They also established a benchmark monoclonal antibody, 2-12C, which provides a standard reference for testing the efficacy of novel therapeutics
By developing a reproducible and physiologically relevant model, The Pirbright Institute has created a shared resource to accelerate the evaluation of novel therapeutics and vaccines aimed at preventing respiratory disease transmission worldwide.
Read the paper: Hatton, C.F., Briggs, E., Polychronakis, E. et al. Aerosol and intranasal delivery of monoclonal antibodies to prevent transmission in pig influenza infection models. npj Vaccines 10, 226 (2025). DOI: https://doi.org/10.1038/s41541-025-01277-9