IFITM3-deficient mice as a model for testing influenza virus vaccines via the intramuscular route

Influenza virus infections remain a significant global health concern. Development of a universal influenza vaccine has been met with challenges, in part due to difficulties with preclinical vaccine testing in mice, which are widely available but are often poorly infected with human and avian influenza viruses. Here, we investigate whether mice lacking interferon-induced transmembrane protein 3 (IFITM3), an antiviral restriction factor, provide a suitable preclinical model for vaccine testing since we observe enhanced replication of multiple influenza virus strains in these mice. We find that IFITM3 KO mice produce a blunted antibody response to intramuscular vaccination that is increased by a booster dose. Nonetheless, their adaptive immune responses to previous infections and vaccinations were found to be functional in limiting weight loss, survival, and viral replication in challenge studies. Overall, our findings identify IFITM3 KO mice as an accessible, functionally immunocompetent preclinical model for assessment of influenza vaccines.