| Summary: | <i>Background:</i> Influenza is a respiratory infection that continues to present a major threat to human health, with ~500,000 deaths/year. Continued circulation of epidemic subtypes in humans and animals potentially increases the risk of future pandemics. Vaccination has failed to halt the evolution of this virus and next-generation prophylactic approaches are under development. Naked, “heat inactivated”, or inert bacterial spores have been shown to protect against influenza in murine models. <i>Methods:</i> Ferrets were administered intranasal doses of inert bacterial spores (DSM 32444<sup>K</sup>) every 7 days for 4 weeks. Seven days after the last dose, the animals were challenged with avian H7N9 influenza A virus. Clinical signs of infection and viral shedding were monitored. <i>Results:</i> Clinical symptoms of infection were significantly reduced in animals dosed with DSM 32444<sup>K</sup>. The temporal kinetics of viral shedding was reduced but not prevented. <i>Conclusion:</i> Taken together, nasal dosing using heat-stable spores could provide a useful approach for influenza prophylaxis in both humans and animals.
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