Legacy of Obesity on Influenza and Coronavirus

总体摘要 我们和其他人已经证明，肥胖会导致疾病严重程度增加，传播时间延长 病毒变异的增加和感染的易感性增加。虽然疫苗仍然是我们最好的预防措施， 接种疫苗对超重/肥胖者的效果较差，导致接种疫苗的肥胖成年人的发病率是 比健康体重的人更容易患上流感。使用我们最新开发的减肥计划来减肥- 诱导肥胖(DIO)小鼠，我们的初步研究表明，接种流感疫苗后的体重减轻 而不是加强保护。同时从高脂肪饮食转向瘦肉控制饮食有效地减轻了体重和 将关键的代谢生物标记物恢复到设定的基线，这并没有改善生存结果。这些发现 有戏剧性的影响，考虑到世界卫生组织(WHO)预测大多数 世界人口生活在超重和肥胖比肥胖更普遍的国家 体重过轻。 肥胖不仅仅是一个BMI数字。这些研究的总体目标是确定新陈代谢 接种疫苗或感染时的状态，而不是BMI，与免疫原性和 预防流感病毒和SARS-CoV-2感染/接种疫苗。我们假设新陈代谢健康在 免疫或感染的时间而不是BMI与保护性免疫反应有关 流感病毒和SARS-CoV-2。为了验证这一假设，我们制定了以下具体目标： 1.证明接种流感疫苗或感染时新陈代谢健康状况的改善会增强 药效和免疫原性。 2.明确肥胖对SARS-CoV-2感染和疫苗接种的影响。 儿童肥胖率和代谢综合征与肥胖无关，预计将呈指数级增长 在接下来的50年里，我们必须制定战略，更好地保护这种增长 人口。如果成功，我们的研究将把代谢生物标记物与疫苗/感染免疫原性和 确定新的保护相关因素。后续研究将确定疫苗平台或干预策略 克服新陈代谢健康状况不佳的方法。我们的创新研究不仅限于流感和新冠肺炎，还包括 可能适用于各种各样的感染/疫苗接种。

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.