Impact of Acute Exercise and Heat Stress on Immune Response to Influenza Vaccination

Purpose: Influenza is a major global health threat, with adults 65+ comprising over a third of related hospitalizations and deaths. In 2022-2023, flu vaccine efficacy against influenza A was only 39% for adults over 18. Certain populations with depressed immune function may turn to adjuvanted vaccines to increase vaccination response. While adjuvanted vaccines like FLUAD enhance immune responses, they often cause side effects, highlighting the need for alternatives like exercise. Regular exercise has been shown to improve vaccine-induced antibody responses without additional adjuvants. Acute bouts of resistance or aerobic exercise before vaccination also boost anti-influenza IgG and IgM titers. We hypothesized that moderate aerobic exercise prior to vaccination enhances immune cell signaling, improving flu vaccine efficacy. In addition, we hypothesize incorporating environmental heat stress into exercise will further enhance the vaccine response by increased LPS activity, a known adjuvant for immune responses. Methods: 34 males (age > 17 yo) completed a 60-minute, moderate intensity (60% HR max ) exercise with (MEH) or without (ME) heat stress on the treadmill, or rest (NE) 24 hours prior to vaccination. LPS and LBP activity, inflammatory cytokines, cortisol, granzyme B and antibody titers were assessed from the venous samples collected from all groups at 5 time points with visits 3, 4, and 5 occurring within 24 hours, 2 weeks, and 4 weeks post vaccination. Results: Environmental conditions differed between ME and MEH, successfully inducing thermal stress in MEH accompanied by significantly higher average and post-exercise rectal temperature (T rec ) (p<0.05). Both groups exercised at 60% HR max , but treadmill speed and RPE were significantly lower in MEH (p<0.05). Circulating LPS levels at PRE60, POST60, and POST24HR showed no significant time (p=0.119) or time*group effects (p=0.124). LBP levels were higher in ME and MEH than NE at POST24HR (p=0.369), with significant time effects (p=0.006) when grouped all together. IL-8 levels showed no group differences at each time point (p>0.05), but time*group effects were significant (p=0.027). Cortisol levels were stable across time except for a POST60 vs. POST24hr increase in ME (p=0.03). Granzyme B levels were consistent across groups (p>0.05). Group and interaction effects, were not significant for A(H1N1) p=0.789; p=0.650), A(H3) (p=0.139; p=0.629), B/Phuket (p=0.203; p=0.636), or B/Brisbane (p=402; p=0.568). All strains demonstrated a significant time effect (A(H1N1), p=0.000; A(H3), p=0.000; B/Phuket, p=0.000; B/Brisbane, p=0.005). Conclusion: Acute exercise intervention and exercise combined with environmental heat stress 24 hours before vaccination does not yield a standard protocol that can serve as an adjuvant increasing influenza vaccine response. Funding source: InCHIP Seed Grant, Faculty Research Fund This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.