Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
Adam McNee, Trevor R.F. Smith, Barbara Holzer, Becky Clark, Emily Bessell, Ghiabe-Henri Guibinga, Heather Brown, Katherine Schultheis, Paul D. Fisher, Stephanie Ramos, Alejandro Núñez, Matthieu Bernard, Simon P. Graham, Veronica Martini, Tiphany Chrun, Yongli Xiao, John C. Kash, Jeffery K. Taubenberger, Sarah T. C. Elliott, Ami Patel, Peter C. L. Beverley, Pramila Rijal, David B. Weiner, Alain Townsend, Kate E. Broderick, Elma Tchilian
Abstract
mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.