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

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.