Strategies to Improve Influenza Vaccine Efficacy in High-Risk Obese Individuals

PROJECT SUMMARY Vaccination is critical for controlling annual influenza epidemics and pandemics, but vaccines are less effective in high-risk populations such as people with obesity. After the 2009 H1N1 pandemic, obesity was identified as an independent high-risk factor for increased influenza disease severity. Work by our lab has shown that obese hosts are not only more susceptible than non-obese hosts to severe influenza disease but also less protected by adjuvanted vaccination. These disconcerting differences highlight the immediate need to develop influenza vaccines that better protect this high-risk group as global obesity rates rise steadily. Our laboratory is using established mouse models of obesity, induced either genetically or by diet, to address this need by investigating strategies to improve vaccine efficacy in obese hosts. We have preliminary data showing that we can rescue the decreased vaccine efficacy in our obese mice by introducing a weight loss intervention 4-weeks before vaccination. This proposal will 1) define the weight-loss "window" required for vaccine efficacy and 2) assess the changes in humoral responses that correlate with vaccine efficacy. This proposal will evaluate the mechanisms behind the increased vaccine efficacy associated with weight loss before immunization. If these mechanisms can be elucidated, adjuvants can be designed to target the same pathways to overcome the problems with the standard of care vaccines. The results of this research will have substantial translational implications for improving vaccine efficacy for other infectious diseases to protect our high-risk populations better and improve public health.