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

• 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
• 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

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.

项目摘要 /摘要 疫苗接种是一种有效的公共卫生措施，但宿主因素包括高龄，性别，肥胖， 身心健康状况可能会影响疫苗功效。佐剂提高了免疫原性 疫苗接种，但通常会导致更大的副作用。作为将佐剂纳入疫苗的替代方案 配方，有证据表明在免疫时进行的体育锻炼可能是 有效的非药理学方法，有可能对次优的人产生更大的影响 免疫反应和反应生成降低。宿主因素对SARS-COV-2免疫反应的影响 长期保护仍有待确定，以及对物理的类似辅助作用的积极发现 运动将立即产生翻译影响。但是，实施的主要障碍 锻炼是不一致的发现和差距，了解基于这种影响的机制。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 对几种不同疫苗可再现的疫苗的反应。这一发现具有 改变疫苗功效，并解决有关免疫反应的宽广和耐用性的问题 基本机制。该应用的目标是确定体育锻炼的程度 在长期抗体和T细胞介导的COVID-19 基于mRNA的疫苗并建立可能具有的个体的免疫增强程度 由于高心理压力引起的次优疫苗反应。另一个目标是确定潜在的手术 机制和引人注目的初步数据显示了与代谢相关机制的希望，这是一种新的 在这个研究领域的方向。 AIM 1将确定当时进行一次练习的程度 初始免疫的塑造对SARS-COV-2 mRNA的免疫反应的幅度，宽度和耐用性 疫苗。结果度量是血清抗尖峰受体结合结构域（RBD）IgG滴度，中和 抗体，抗原特异性CD4+和CD8+ T细胞反应，最高至一年免疫后。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覆盖任何潜力的程度 压力的影响。 AIM 3将采用转录组（RNA-SEQ）和代谢组（Raman）措施来识别 运动影响免疫反应对疫苗接种的途径。这项研究的长期目标 方向是完善和制定行为干预措施，以优化免疫力并更广泛地应用 关于免疫原性的关键途径学到的发现，以优化疫苗开发 目前服务不足的人群。