Publication date: Oct 01, 2026
Vaccination under deliberately varied metabolic conditions provides a framework to identify metabolic determinants of immune response to vaccine and to identify metabolic pathways that may serve as immunomodulators or future adjuvant targets. Suboptimal vaccine immunogenicity and waning antibody durability remain significant public health challenges requiring effective interventions. To examine the association between vaccine immunogenicity and altered metabolic microenvironments, we applied a short-term metabolic intervention coinciding with SARS-CoV-2 immunization. In this randomized trial, half of the participants completed a metabolically targeted 90-min exercise bout immediately post-immunization, a stimulus known to induce sustained shifts in systemic metabolic changes for up to 24 h. Participants in the control group did not exercise after vaccination. Serum anti-RBD IgG antibody and a putative biomarker of germinal center activity (CXCL13) were assessed as measures of immunogenicity in longitudinally collected samples, and metabolic profile was analyzed by Raman spectroscopy. Associations between age, BMI, psychosocial stress and immune response and metabolic profiles were determined. The exercise-metabolic treatment enhanced antibody durability and shifted the kinetics of CXCL13 and serum antibody response in participants without pre-existing immunity. Specific immuno-metabolic signatures distinguished exercise-metabolic treatment from control, identified participants with pre-existing immunity, and revealed effects of age. This study demonstrates the feasibility of a readily accessible short-term metabolic intervention applied at vaccination in shaping in vivo adaptive immunity and provides critical insights into metabolic predictors of immunogenicity. These findings can be used to interrogate further host factor-related metabolic predictors of vaccine response (i. e., age, BMI, stress) and develop innovative vaccine platforms that influence the metabolic microenvironment.