Sex-specific effects of obesity on influenza A virus pathogenesis and vaccine response 9083

Abstract Description We investigated if obesity impacts influenza A virus (IAV) pathogenesis and influenza vaccine responses in a sex-specific manner, using a high-fat diet-induced obese mouse model. Following a sublethal dose infection with A/California/04/2009 H1N1 IAV, mice with obesity had greater body mass loss than the non-obese mice, and females had severe morbidity than male mice. Of the four groups, females with obesity suffered with the most severe disease following IAV infection and 25% of them also reached the humane endpoint, which was associated with dysregulated inflammatory responses rather than the pulmonary virus replication. Additionally, following vaccination with an inactivated A/California/04/2009 H1N1 IAV vaccine, antibody titers were higher in females than in male mice, irrespective of obesity. Importantly, males with obesity had the lowest levels of antibody titers among the four groups and were least protected following IAV challenge, which was associated with a reduced frequencies of plasma cells in the bone marrow. These studies suggest that obesity exerts its impact on influenza pathogenesis and vaccine responses in a sex-specific manner where females with obesity suffer with severe disease following IAV infection and the males with obesity are less protected after influenza vaccination. Funding Sources Supported by the NIGMS/NIH through the Center on Emerging and Zoonotic Infectious Diseases (CEZID) at KSU (#P20GM130448). Topic Categories Viral Immunology (VIR)