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.