Eddy Adrian C, Speaks Samuel, Roth Megan, Roettger Jack E, Reznik Brendan M, Mohan Shreenath, Liu Ben D, Hemann Emily A, Yount Jacob S
Department of Microbial infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
Department of Microbial infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
Vaccine. 2025 Jul 8;62:127458. doi: 10.1016/j.vaccine.2025.127458.
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.
流感病毒感染仍然是全球重大的健康问题。通用流感疫苗的研发面临挑战，部分原因是在小鼠中进行临床前疫苗测试存在困难，小鼠虽广泛可得，但通常很难感染人类和禽流感病毒。在此，我们研究缺乏抗病毒限制因子干扰素诱导跨膜蛋白3（IFITM3）的小鼠是否能提供一个合适的临床前疫苗测试模型，因为我们观察到多种流感病毒株在这些小鼠中复制增强。我们发现，IFITM3基因敲除小鼠对肌肉注射疫苗产生的抗体反应减弱，而加强剂量可增强这种反应。尽管如此，在攻毒研究中发现它们对先前感染和疫苗接种的适应性免疫反应在限制体重减轻、生存和病毒复制方面具有功能。总体而言，我们的研究结果表明，IFITM3基因敲除小鼠是一种可用于评估流感疫苗的、功能上具有免疫活性的临床前模型。
