Risk of Influenza Infection In A Vaccinated Obese Population

描述（由申请人提供）：流感病毒感染是全球范围内大量发病率和死亡率的原因。在非大流行年份，美国10 - 20%的人口感染流感病毒。在任何一年，超过120，000人住院，36，000美国人死于流感和流感相关并发症。在流感大流行的情况下，这些发病率和死亡率指标中的每一项都会大大增加。最近有报道称，大流行性H1N1流感导致肥胖人群的发病率和死亡率增加，因此确定肥胖个体是否处于流感疫苗失效的增加风险中是极其重要的。我们的初步数据表明，与健康体重个体相比，肥胖个体在接种疫苗后随着时间的推移流感特异性抗体下降更快。此外，与健康体重个体相比，肥胖个体的细胞毒性T淋巴细胞（CD8+）对流感抗原刺激的反应较差。本申请旨在确定与健康体重接种个体相比，肥胖人群是否具有更高的流感感染率和更严重的症状。与年轻人群相比，老年人群具有更高的疫苗失败率，并且在老年人中观察到的许多免疫功能障碍（抗体应答降低，T细胞反应性受损）也在肥胖人群中发现。这表明，与老龄化人口类似，肥胖人群可能对流感疫苗接种反应不足。我们的研究将回答以下与肥胖人群中疫苗反应性相关的问题：流感疫苗接种是否不能保护肥胖人群免受流感感染，其程度与健康体重人群相同？在接种疫苗的肥胖人群中，抗体滴度随时间下降的速度有多快？肥胖个体对疫苗接种的CD8 T细胞应答降低的机制基础是什么？如果我们确定肥胖与流感疫苗免疫应答受损和对流感感染的保护降低有关，这将表明我们需要重新评估我们的疫苗接种计划，不仅是流感，而且可能是其他病原体，在日益肥胖的美国人口中。

DESCRIPTION (provided by applicant): 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.