Aerosol and intranasal delivery of monoclonal antibodies to prevent transmission in pig influenza infection models
There is an urgent need for robust animal models to assess novel therapies that prevent the transmission of respiratory pathogens. We developed two complementary pig influenza models, direct and contact challenge, to evaluate the ability of monoclonal antibodies to block transmission. Using the strongly neutralizing 2-12 C mAb targeting H1N1pdm09 haemagglutinin, we established a benchmark for comparing mAb delivery routes and platforms. Intravenous administration of 2-12 C consistently showed the highest efficacy in the direct challenge model. The contact influenza challenge model, which best mimics natural exposure, was further optimized by evaluating key parameters, including timing of co-housing, infectious dose, and delivery routes. Aerosol and intravenous delivery of 2-12 C were equally potent, preventing infection in contact animals, while intranasal delivery prevented infection in some but not all animals. The pig direct and contact influenza challenge models provide powerful platforms for the evaluation therapeutic strategies to prevent influenza disease and transmission in humans.
Authors
- Ellen C. Moorhouse
- Ai-xing Guan
- Emily Briggs (ORCID: https://orcid.org/0000-0002-3606-9427)
- Catherine F. Hatton (ORCID: https://orcid.org/0000-0003-4138-5309)
- Shathviga Manoharan (ORCID: https://orcid.org/0000-0001-7382-9766)
- Alain Townsend (ORCID: https://orcid.org/0000-0002-3702-0107)
- Francisco J. Salguero (ORCID: https://orcid.org/0000-0002-5315-3882)
- Ronan MacLoughlin (ORCID: https://orcid.org/0000-0002-3164-1607)
- Pramila Rijal (ORCID: https://orcid.org/0000-0002-9214-9851)
- Elma Tchilian (ORCID: https://orcid.org/0000-0002-4869-5118)
- Ashutosh Vats (ORCID: https://orcid.org/0000-0002-9245-4266)
- Ehsan Sedaghat-Rostami
- Bhawna Sharma (ORCID: https://orcid.org/0000-0002-4570-2335)
- Sanis Wongborphid
- Tiphaine Cayol
- Basudev Pauydal
- Eleni Polychronakis
Institutions
- The Pirbright Institute (GB)
- John Radcliffe Hospital (GB)
- University of Surrey (GB)
- University of Manchester (GB)
- University of Oxford (GB)
- Aerogen (Ireland) (IE)
- MRC Weatherall Institute of Molecular Medicine (GB)
- MRC Human Immunology Unit (GB)
- Science Oxford (GB)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-11-05
- DOI
- https://doi.org/10.1038/s41541-025-01277-9
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- UK Research and Innovation
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council