The purpose of this study is to evaluate the extent to which a single 90-minute session of light to moderate intensity exercise performed within 30 minutes after receiving the initial dose of COVID-19 mRNA vaccine may modify the immune response to vaccination and identify potential underlying mechanisms. A secondary goal is to establish whether psychosocial stress, resilience or depression measures are associated with immune response to vaccination. Participants will be randomly assigned to either an exercise post-vaccine condition (intervention group) or a daily routine as usual but with no exercise condition (control group). Blood samples will be collected from participants before the initial COVID vaccine. At this first visit, participants will be given several psychosocial surveys to complete, the 14-item Perceived Stress Scale , the 25-item Resilience Scale, and the Patient Health Questionnaire. Participants will also be given a copy of local mental health resources. All participants will be asked to complete the psychosocial surveys on the day before or the day of vaccination.

On the day the initial COVID-19 mRNA vaccine is administered, participants assigned to the exercise group will meet with research study personnel within 30 minutes after receiving the vaccine at or near the location at which the vaccine is administered. Participants will begin a light to moderate intensity exercise session consisting of brisk walking, alternating walk/jog, or light jog dependent upon the aerobic fitness level of the participant. The intensity of exercise will be adjusted by heart rate and/or the Borg Rating of Perceived Exertion (RPE) 6-20 scale such that heart rate is approximately 70% of age-adjusted maximal heart rate (220-age), a range between 120-140 beats per minute for most participants, at an RPE of 11 (light) - 13 (somewhat hard). Heart rate and RPE will be monitored approximately every 10 minutes and workload will be adjusted by verbal coaching if necessary. Water and light snacks will be freely available throughout exercise. Participants assigned to the daily routine as usual group will be instructed to continue with their day as typical but to avoid exercise on the day of immunization.

All participants will be given a copy of the appropriate Vaccine Information Fact Sheet and three side effect report forms which list the side effects described in the Vaccine Information sheet. All participants will be asked to record side effects on the appropriate form every 24 hours for the first 72 hours after receiving the initial vaccine. Any concerning side effects are to be reported to study personnel, and the participants will be reminded to report such side effects to their health care provider.

Participants will be asked to return for blood collection seven days, approximately one month, and at three, six, and 12 months following vaccination. Serum from blood samples will be frozen for analysis of serum antibody (anti-receptor binding domain IgG) and neutralizing antibody. Peripheral blood mononuclear cells will be frozen from samples collected at seven days, three or six months post-immunization. The ex vivo functions of Severe Acute Respiratory Syndrome Coronavirus 2 specific T cells specific for dominant epitopes will be evaluated by the assessment of intracellular cytokine production profiles using Severe acute respiratory syndrome coronavirus 2 spike peptide pools. Other peripheral blood mononuclear cells will be reserved for RNA-sequencing (RNA-Seq) analysis. Gene expression will be assessed with RNA-Seq (single cell). The RNA-Seq data analysis will be performed by the Genome Informatics Facility (differential gene expression), GO and Kegg pathway analysis) for comparisons between exercise and control participants. Raman analysis will be used to assess metabolite profile in serum.

The frequency of antigen specific T cells expressing interferon-gamma, tumor necrosis factor alpha, or interleukin-2 or multi-cytokine producing cells, serum antibody and neutralizing antibody will be compared between exercise and control participants. Statistical Package for the Social Sciences (SPSS) software will be used in analyses. As a secondary goal, discovery-based analysis to examine potential effects of psychosocial factors will be performed initially with bivariate analysis of survey scores and immune outcome measures (antibody and T cell cytokines). If a significant correlation between psychosocial survey score and an immune outcome measure is observed, additional follow up with regression model analyses to identify the extent to which separate factors contribute to a given immune outcome measure.