Live attenuated influenza virus vaccine protects obese mice

Abstract

Abstract Fifty percent of the United States population is predicted to be obese (body mass index > 30) by 2030. Obese individuals are considered a high-risk group for developing severe influenza disease. To compound this, studies have shown that inactivated influenza vaccination has decreased efficacy in this high-risk population. However, the efficacy of live-attenuated vaccines has not been investigated to date. Therefore, we sought to determine if a cold-adapted A/California/04/2009 (caCA/09) H1N1 influenza virus vaccine protected obese mice from lethal influenza virus challenge. In these studies, we demonstrate that intranasal administration of caCA/09 vaccine protected genetically and diet-induced obese (DIO) mice from a lethal challenge with wild-type influenza virus (CA/09) 4 weeks post-vaccination. Protection was not due to route of administration, as intranasal vaccination with inactivated caCA/09 virus was not protective. Unlike non-vaccinated obese mice, caCA/09 vaccinated obese mice cleared the virus and controlled viral spread, as determined by lung TCID50 and immunohistochemistry, respectively. Protection of obese mice lasts at least 17 weeks post-vaccination. Mechanistically, we found that effector memory CD4 and CD8 T cells were increased in lungs of vaccinated mice that may provide heterosubtypic protection. Indeed, the vaccinated obese mice were protected from a lethal challenge with an H5 deselected influenza virus. In conclusion, live-attenuated virus vaccination is a viable option to protect obese hosts against increased disease severity and mortality.