Legacy of Obesity on Influenza and Coronavirus

OVERALL ABSTRACT We and others have demonstrated that obesity results in enhanced disease severity, prolonged transmission of viral variants and increased susceptibility to infection. While vaccines remain our best prevention, vaccination is less effective in overweight/obese people resulting in vaccinated obese adults being twice as likely to develop flu than healthy weight people. Using our newly developed weight loss program for diet- induced obese (DIO) mice, our preliminary studies suggest that weight loss following flu vaccination does not improve protection. While switching from a high fat to lean control diet effectively reduced weight and returned key metabolic biomarkers to a set baseline, this did not improve survival outcomes. These findings have dramatic ramifications considering that the World Health Organization (WHO) predicts that most of the world's population lives in countries where being overweight and obese is more prevalent than being underweight. Obesity is more than a BMI number. The overall goals of these studies are to determine if the metabolic state at the time of vaccination or infection, rather than BMI, are tightly correlated with immunogenicity and protection from influenza virus and SARS-CoV-2 infection/vaccination. We hypothesize that metabolic health at the time of immunization or infection and not BMI, correlates with protective immune responses against influenza virus and SARS-CoV-2. To test this hypothesis, we have developed the following specific aims: 1. Demonstrate that improved metabolic health at the time of influenza vaccination or infection enhances efficacy and immunogenicity. 2. Define the legacy of obesity on SARS-CoV-2 infection and vaccination. With rates of childhood obesity and metabolic syndrome independent of obesity, predicted to exponentially increase over the next 50 years, it is imperative that we develop strategies to better protect this growing population. If successful, our studies will link metabolic biomarkers to vaccine/infection immunogenicity and identify novel correlates of protection. Follow up studies will identify vaccine platforms or intervention strategies that overcome poor metabolic health. Our innovative studies extend beyond influenza and COVID-19 and are likely to apply to a wide variety of infections/vaccinations.