Infection with influenza virus is responsible for a great deal of morbidity and mortality worldwide. In non-pandemic years, 10-20% of the population in the US is infected with influenza virus. In any given year, more than 120,000 persons are hospitalized and 36,000 Americans die from influenza and influenza-related complications. In the case of an influenza pandemic, each of these measures of morbidity and mortality would greatly increase. With the recent report that pandemic H1N1 influenza causes increased morbidity and mortality in an obese population, it is extremely important to determine if obese individuals are at an increased risk for influenza vaccine failure. Our preliminary data demonstrates that obese individuals have a steeper drop influenza specific antibody over time following vaccination compared with healthy weight individuals. In addition, cytotoxic T lymphocytes (CD8+) from obese individuals have a poorer response to influenza antigen stimulation in comparison with healthy weight individuals. This application is designed to determine if the obese population will have a higher rate of influenza infection and more severe symptoms when compared with healthy weight vaccinated individuals The elderly population has a higher rate of vaccine failure compared to a younger population, and many of the immune dysfunctions seen in the elderly (reduced antibody responses, impaired T cell reactivity) have also been found in the obese. This suggests that, similar to an aging population, an obese population may not respond adequately to flu vaccination. Our study will answer the following questions relating to vaccine responsiveness in an obese population: Does influenza vaccination fail to protect obese individuals from influenza infection to the same degree as healthy weight individuals? How rapidly does the antibody titer drop over time in a vaccinated obese population? What is the mechanistic basis for the diminished CD8 T cell response to vaccination in an obese individual? If we determine that obesity is associated with an impaired immune response to influenza vaccination and decreased protection against influenza infection, this would suggest that we need to re-evaluate our vaccination program, not only for influenza, but perhaps for other pathogens as well, in an increasingly obese US population. PUBLIC HEALTH RELEVANCE: Rates of obesity are increasing rapidly worldwide resulting in major impacts on health status and disease prevention. Additionally, the threat of pandemic influenza has grown in recent years with the discovery of new strains and an increasingly susceptible population. Determination of influenza vaccination effectiveness in the obese population will provide an invaluable resource in determining the best way to prevent the initiation and spread of any forthcoming influenza pandemic and provide new insights into the effect of obesity on function of the immune system.