Dirty Mice Have Altered Influenza A Virus Clearance And Lesions Compared To SPF Mice: A Proposed Model For Study Of Vaccine Response In Humans

Abstract

Influenza A virus (IAV) is a seasonal pathogen that causes annual morbidities and mortalities. Current vaccines often exhibit reduced efficacy to seasonal strains and offer limited protection to novel pandemics. Additionally, vaccines that are successful in mice often fail to translate to humans. This could be due to the nature of the mouse model housed in specific pathogen free (SPF) conditions. Humans are exposed to a variety of pathogens that SPF mice are protected from. Unlike SPF mice, the immune system of pet store mice more closely recapitulates the immune system of humans. When SPF mice are co‐housed with pet store mice harboring natural mouse pathogens, termed dirty mice, these mice obtain phenotypes observed in the human immune system. In order to determine if dirty mice are an improved mouse model for vaccine development/testing, we sought to study IAV disease in dirty mice. We infected control or dirty mice with IAV and assessed viral clearance and pathology. We observed reduced IAV clearance and enhanced airway pathology characterize by denuded and sloughed/necrotic airway epithelium in dirty mice. These data demonstrate the importance of studying IAV in the dirty mouse model to facilitate more effective vaccine development and testing to improve translation to humans.Support or Funding InformationNIH