Risk of Influenza Infection In A Vaccinated Obese Population

描述（由申请人提供）：流感病毒感染是造成全球大量发病率和死亡率的原因。在非大流行年份，美国有10-20%的人口感染流感病毒。在任何一年，都有超过12万人住院，3.6万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将大大增加。由于预计在不久的将来会爆发大流行性流感，确定肥胖个体接种疫苗失败的风险是否增加是极其重要的。几项已发表的研究表明，肥胖成人对接种乙肝疫苗的抗体反应减弱，肥胖儿童对接种破伤风疫苗的抗体反应减弱，肥胖成人的初步数据也表明，肥胖个体流感疫苗失败率更高的风险增加。该建议旨在确定肥胖人群对流感疫苗接种的反应是否减弱。与年轻人群相比，老年人群的疫苗失败率更高，而且在老年人中发现的许多免疫功能障碍（抗体反应降低，T细胞反应性受损）也在肥胖人群中发现。这表明，与人口老龄化类似，肥胖人群可能对流感疫苗没有充分的反应。我们的研究将回答以下与肥胖人群的疫苗反应性有关的问题：流感疫苗接种对肥胖人群免受流感感染的保护程度是否与瘦人群相同？通过抗体的产生和T细胞对流感抗原的反应能力来衡量，肥胖人群对流感疫苗的反应是否受损？在肥胖个体中发现的慢性炎症应激蛋白的水平和/或特征能否区分对流感疫苗有反应的人和对流感疫苗没有反应的人？如果我们确定肥胖与流感疫苗免疫反应受损和对流感感染的保护能力下降有关，这将表明我们需要重新评估我们的疫苗接种计划，不仅针对流感，也可能针对其他病原体，在日益肥胖的美国人口中。公共卫生相关性：全世界的肥胖率正在迅速上升，对健康状况和疾病预防产生重大影响。此外，近年来随着新毒株的发现和易感人群的增加，大流行性流感的威胁有所增加。确定肥胖人群的流感疫苗接种有效性将为确定预防任何即将到来的流感大流行的发生和传播的最佳方法提供宝贵的资源，并为肥胖对免疫系统功能的影响提供新的见解。

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 expectation of a pandemic influenza outbreak in the near future, it is extremely important to determine if obese individuals are at an increased risk for vaccine failure. Several published studies showing diminished antibody response to vaccination with hepatitis B in obese adults and diminished antibody response to tetanus vaccination in obese children and our own preliminary data in obese adults, suggests that obese individuals are at increased risk for higher rates of influenza vaccine failure. This proposal is designed to determine if the obese population has a diminished response to influenza vaccination. 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 protect an obese population from influenza infection to the same degree as a lean population? Is the response to influenza vaccine, measured by production of antibody as well as the ability of T cells to respond to influenza antigen, impaired in an obese population? Can levels and/or characteristics of the chronic inflammatory stress proteins found in obese individuals differentiate between those who respond to influenza vaccination and those that don't? 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.