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 病毒变异和感染易感性增加。虽然疫苗仍然是我们最好的预防措施， 疫苗接种对超重/肥胖人群的效果较差，导致接种疫苗的肥胖成年人的患病率是肥胖成年人的两倍 比健康体重的人更容易患流感。使用我们新开发的减肥计划进行饮食- 诱导性肥胖（DIO）小鼠，我们的初步研究表明，流感疫苗接种后体重减轻确实 不能提高防护能力。从高脂肪饮食转向瘦肉控制饮食的同时有效减轻了体重和 将关键代谢生物标志物恢复到设定的基线，但这并不能改善生存结果。这些发现 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 体重不足。 肥胖不仅仅是 BMI 数字。这些研究的总体目标是确定代谢是否 接种疫苗或感染时的状态，而不是体重指数，与免疫原性密切相关， 预防流感病毒和 SARS-CoV-2 感染/疫苗接种。我们假设代谢健康状况 免疫或感染的时间，而不是体重指数，与针对病毒的保护性免疫反应相关 流感病毒和 SARS-CoV-2。为了检验这一假设，我们制定了以下具体目标： 1. 证明在接种流感疫苗或感染时代谢健康的改善可以增强 功效和免疫原性。 2. 明确肥胖对 SARS-CoV-2 感染和疫苗接种的影响。 与肥胖无关的儿童肥胖和代谢综合征的发病率预计呈指数级增长 随着未来 50 年的增长，我们必须制定战略来更好地保护这一不断增长的 人口。如果成功，我们的研究将把代谢生物标志物与疫苗/感染免疫原性联系起来， 确定新的保护相关性。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问题。我们的创新研究不仅限于流感和 COVID-19， 可能适用于多种感染/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.