Legacy of Obesity on Influenza and Coronavirus

肥胖对流感和冠状病毒的影响

• 批准号: 10355239
• 负责人: Stacey L Schultz-Cherry
• 金额: $ 9.1万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355239
• 关键词: 2019-nCoV; ACE2; Adolescent; Adult; Biological Markers; Biological Models; Body Weight decreased; Body mass index; COVID-19; Cells; Child; Coronavirus; Country; Disease; Ethnic group; Fatty acid glycerol esters; Female; Follow-Up Studies; Goals; Health; Hemagglutination; Immune; Immune response; Immunization; Immunize; Infection; Inflammation; Influenza; Influenza vaccination; Intervention; Knowledge; Leptin; Link; Metabolic; Metabolic syndrome; Modeling; Mus; Obese Mice; Obesity; Overweight; Persons; Phenotype; Population; Predisposition; Prevalence; Prevention; Prognostic Marker; Race; Risk Factors; SARS-CoV-2 infection; Severity of illness; Testing; Thinness; Time; Transgenic Mice; Underweight; United States; Vaccinated; Vaccination; Vaccines; Variant; Viral; Virus; Weight; World Health Organization; adiponectin; adult obesity; base; diet-induced obesity; dietary control; epidemiologic data; flu; healthy weight; high risk; immunogenicity; improved; influenza infection; influenzavirus; innovation; male; metabolic phenotype; mouse model; novel; obese person; obesity in children; seroconversion; socioeconomics; survival outcome; vaccine efficacy; vaccine platform; vaccine response; viral transmission; weight loss program

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.

总体抽象 我们和其他人已经证明肥胖会导致疾病严重程度增加，延长传播 病毒变异和增加感染的敏感性。虽然疫苗仍然是我们最好的预防 疫苗接种对超重/肥胖的人的有效性较小，导致肥胖的成年人是两倍 可能会发展流感比健康的体重人。使用我们新开发的减肥计划进行饮食 - 诱导肥胖（DIO）小鼠，我们的初步研究表明流感疫苗后的体重减轻 不能改善保护。从高脂肪切换到瘦饮食的同时，有效地减轻了体重和 将主要的代谢生物标志物返回到设定的基线，这并不能改善生存结果。这些发现 考虑到世界卫生组织（谁）预测，大多数 世界人口生活在超重和肥胖的国家中比成为 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是否 疫苗接种或感染时而不是BMI的状态与免疫原性紧密相关， 防止影响力病毒和SARS-COV-2感染/疫苗接种。我们假设这种代谢健康 免疫化或感染而非BMI的时间，与受保护的免疫反应相关 流感病毒和SARS-COV-2。为了检验这一假设，我们已经开发了以下特定目的： 1。证明在影响力疫苗接种或感染增强时的代谢健康改善 功效和免疫原性。 2。定义SARS-COV-2感染和疫苗接种的肥胖症的遗产。 与肥胖无关的儿童肥胖和代谢综合征的发生率，预计为指数 在接下来的50年中，我们必须制定策略以更好地保护这一增长 人口。如果成功，我们的研究将将代谢生物标志物与疫苗/感染免疫原性和 识别新颖的保护相关性。后续研究将确定疫苗平台或干预策略 这克服了不良的代谢健康。我们的创新研究范围超出了影响力和Covid-19，并且是 可能适用于多种感染/疫苗接种。