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.

项目总结/摘要 接种疫苗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， 身体或心理健康状况可能影响疫苗的效力。佐剂改善免疫原性， 接种疫苗，但往往会产生更大的副作用。作为疫苗中包含佐剂的替代品 有证据表明，在免疫接种时进行的体育锻炼可能是一种预防免疫接种的方法。 有效的非药理学方法，可能对次优个体产生更大影响 免疫应答和降低的反应原性。宿主因素对SARS-CoV-2免疫应答的影响 和长期的保护仍有待建立，和积极的发现，一个类似的影响，物理 运动会产生直接的转化效果。然而，执行《公约》的主要障碍是： 然而，在对这些影响的机制的认识方面存在着不一致的结论和空白。我们 最近的出版物表明，我们已经确定了一种运动方案， 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 改变疫苗效力，解决免疫反应的广度和持久性问题， 基本机制。这个应用程序的目标是确定体育锻炼的程度 在对COVID-19的长期抗体和T细胞介导的免疫应答中表现出类似于解毒剂的作用 基于mRNA的疫苗，并确定可能有免疫缺陷的个体的免疫增强程度。 由于心理压力大，疫苗反应不佳。另一个目标是确定潜在的操作 机制，令人信服的初步数据显示，代谢相关机制的承诺，一个新的 在这个研究领域的方向。目标1将确定当时一次练习的应用程度 初始免疫的大小决定了对SARS-CoV-2 mRNA的免疫应答的大小、广度和持久性 疫苗结果指标为血清抗棘突受体结合域（RBD）IgG滴度，中和 抗体、抗原特异性CD 4+和CD 8 + T细胞应答在免疫后一年内测量。目的2 将确定心理应激对抗体和抗原特异性CD 4+和CD 8 + T细胞的影响 对SARS-CoV-2免疫的免疫反应以及运动可能压倒任何潜在影响的程度 压力的影响。目标3将应用转录组学（RNA-Seq）和代谢组学（拉曼）方法来鉴定 运动影响对疫苗接种的免疫反应的途径。这项研究的长期目标是 方向是完善和开发优化免疫力的行为干预措施，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。