Adjuvant effect of physical exercise on immune response to COVID-19 vaccination and interactions with stress

体育锻炼对 COVID-19 疫苗接种免疫反应的辅助作用以及与压力的相互作用

基本信息

批准号：
10593597
负责人：
Marian L Kohut
金额：
$ 22.49万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-06 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593597
关键词：
2019-nCoV Acute Address Adjuvant Antibodies Antibody Response Antigens Behavior Therapy Body Weight Buffers CD8-Positive T-Lymphocytes COVID-19 COVID-19 vaccination COVID-19 vaccine Cellular Metabolic Process Chronic Complex Critical Pathways Data Dendritic Cells Dose Elderly Exercise Exhibits Formulation Gene Expression Glucocorticoids Goals Health Status Helper-Inducer T-Lymphocyte Immune Immune response Immunity Immunization Immunoglobulin G Immunologic Memory Impairment Individual Integration Host Factors Knowledge Learning Literature Maps Measures Mental Health Messenger RNA Metabolic Metabolism Modeling Moderna COVID-19 vaccine Obesity Outcome Measure Pathway interactions Patient Self-Report Pfizer-BioNTech COVID-19 vaccine Physical Exercise Population Positioning Attribute Protocols documentation Psychological Stress Psychosocial Stress Public Health Publications RNA vaccine Raman Spectrum Analysis Reporting Reproducibility Research Serum Shapes Standardization Stress Surveys T cell response T memory cell T-Lymphocyte Time Underserved Population Vaccination Vaccines bench-to-bedside translation cell mediated immune response cytokine field study human old age (65+)immune activation immunogenicity implementation barriers improved insight metabolic profile metabolomics neutralizing antibody novel pathogen perceived stress physical conditioning receptor binding response sex side effect transcriptome sequencing transcriptomics translational applications translational impact vaccine development vaccine efficacy vaccine formulation vaccine immunogenicity vaccine response

项目摘要

PROJECT SUMMARY / ABSTRACT Vaccination is an effective public health measure, yet host factors including advanced age, sex, obesity, physical or mental health status may influence vaccine efficacy. Adjuvants improve immunogenicity to vaccination but often result in greater side effects. As an alternative to the inclusion of adjuvants in the vaccine formulation, evidence suggests physical exercise performed at the time of immunization may serve as an effective non-pharmacological approach with the potential for greater impact in individuals with suboptimal immune response and reduced reactogenicity. The effect of host factors on immune response to SARS-CoV-2 and long-term protection remains to be established, and positive findings for an adjuvant-like effect of physical exercise would have an immediate translational impact. However, major barriers to the implementation of exercise are inconsistent findings and a gap in the knowledge of the mechanisms that underlie such effects. Our recent publication shows that we have identified an exercise protocol that consistently increases antibody response to vaccines that is reproducible across several different vaccines. This finding holds the potential to transform vaccine efficacy and address questions on the breadth and durability of immune response and underlying mechanisms. The goals of this application are to determine the extent to which physical exercise exhibits an adjuvant-like effect across long-term antibody and T cell-mediated immune responses to COVID-19 mRNA-based vaccines and establish the degree of immune enhancement in individuals who may have suboptimal vaccine response due to high psychological stress. An additional goal is to identify potential operative mechanisms, and compelling preliminary data show promise for metabolism-related mechanisms, a new direction in this field of study. Aim 1 will identify the extent to which a single exercise session applied at the time of initial immunization shapes the magnitude, breadth, and durability of immune response to SARS-CoV-2 mRNA vaccine. Outcome measures are serum anti-spike receptor-binding domain (RBD) IgG titer, neutralizing antibody, antigen-specific CD4+ and CD8+ T cell response measured up to one-year post-immunization. Aim 2 will determine the influence of psychological stress on antibody and antigen-specific CD4+ and CD8+ T cell immune response to SARS-CoV-2 immunization and the extent to which exercise may override any potential effect of stress. Aim 3 will apply transcriptomic (RNA-Seq) and metabolomic (Raman) measures to identify pathways by which exercise influences immune response to vaccination. The long-term goals of this research direction are to refine and develop behavioral interventions that optimize immunity and more broadly apply the findings learned with respect to critical pathways of immunogenicity to optimize vaccine development for currently underserved populations.

项目概要/摘要疫苗接种是一项有效的公共卫生措施，但宿主因素包括高龄、性别、肥胖、身体或心理健康状况可能会影响疫苗的功效。佐剂可提高免疫原性接种疫苗，但往往会导致更大的副作用。作为疫苗中包含佐剂的替代方案公式化，有证据表明，在免疫接种时进行的体育锻炼可以作为有效的非药物方法，有可能对亚健康个体产生更大的影响免疫反应和反应原性降低。宿主因素对 SARS-CoV-2 免疫反应的影响长期保护作用仍有待建立，并且物理治疗具有类似佐剂作用的积极发现锻炼将产生立竿见影的转化影响。然而，实施的主要障碍运动的结果不一致，而且对造成这种影响的机制的了解存在差距。我们的最近的出版物表明，我们已经确定了一种持续增加抗体的运动方案对疫苗的反应在几种不同的疫苗中是可重复的。这一发现有可能转变疫苗功效并解决免疫反应的广度和持久性问题底层机制。此应用程序的目标是确定体育锻炼的程度在针对 COVID-19 的长期抗体和 T 细胞介导的免疫反应中表现出佐剂样作用基于 mRNA 的疫苗并确定可能患有以下疾病的个体的免疫增强程度由于心理压力过大，疫苗反应欠佳。另一个目标是确定潜在的操作人员机制和令人信服的初步数据显示了代谢相关机制的前景，这是一种新的机制该领域的研究方向。目标 1 将确定当时单次锻炼的应用程度初始免疫的影响决定了对 SARS-CoV-2 mRNA 免疫反应的程度、广度和持久性疫苗。结果测量包括血清抗尖峰受体结合域 (RBD) IgG 滴度、中和抗体、抗原特异性 CD4+ 和 CD8+ T 细胞反应在免疫后一年内进行测量。目标2 将确定心理压力对抗体和抗原特异性 CD4+ 和 CD8+ T 细胞的影响对 SARS-CoV-2 免疫的免疫反应以及运动可能会压倒任何潜在的免疫反应的程度压力的影响。目标 3 将应用转录组学 (RNA-Seq) 和代谢组学 (拉曼) 措施来识别运动影响疫苗接种免疫反应的途径。本研究的长期目标方向是完善和开发行为干预措施，以优化免疫力并更广泛地应用关于免疫原性关键途径的研究结果，以优化疫苗开发目前服务不足的人群。