Could Exercise Be a Behavioral Adjuvant for Vaccines?
Could Exercise Be a Behavioral Adjuvant for Vaccines?
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Physical activity is one of the key components of living a healthy lifestyle. The benefits of regularly moving your body are numerous, including improved mood, energy levels, protection against various diseases and better quality of sleep. During the lockdowns enforced throughout the COVID-19 global pandemic, many people relied on exercise to promote good physical and mental health.
Over recent decades, the impact that physical activity – in varying intensities – has on the constituents of the human immune system has become increasingly recognized. Moderate-intensity exercise has been found to stimulate cellular immunity, and in regular exercise practices, inflammatory responses and stress hormones are decreased. In contrast, high-intensity practices – without sufficient rest – can decrease cellular immunity, increasing the risk of infection and disease occurring.
Considering the impact that physical activity has on the naturally occurring immune system, researchers have questioned how physical activity might affect the immune response induced by vaccination.
Iowa State University researchers conducted a recent study exploring whether mild- to moderate-intensity exercise – directly after a flu or SARS-CoV-2 vaccine – provided an “extra boost”. The study, published in Brain, Behavior and Immunity, revealed that cycling on a stationary bike or taking a brisk walk for 90-minutes post-vaccination resulted in increased antibody production in the following 4-weeks compared to controls. A shorter, 45-minute bout of exercise was not found to induce the same effects.
Participants in the research had a wide range of body mass indexes (BMI) and fitness levels. Maintaining a specific heart rate – rather than achieving a set distance – was a key focus during physical activity. Consequently, the study findings are likely to be applicable across wider populations, the researchers say.
At this stage, the scientists can’t confirm why the increased antibody production was observed in the 90-minute physical activity group, as the underlying physiological mechanisms are unclear. Nonetheless, the study suggests that exercise could be a potential adjuvant for vaccines.
Technology Networks interviewed the lead author of the study, Professor Marian Kohut, to understand how the research was conducted, the applications of this work and the next steps for the team.
Molly Campbell (MC): What inspired you to conduct this research?
Marian Kohut (MH): This research was based on findings from some previous experiments in which Justus Hallam had found that 90-minutes of exercise enhances the ability of immune cells (dendritic cells) to produce a protein (IFNα) that appears to play a role in the antibody response to infection or vaccination.
MC: Can you talk about the types of vaccines that you analyzed in this study, and how the antibody responses post-exercise differed/ were similar across each type?
MH: In humans, we evaluated antibody responses to two different inactivated virus vaccines: monovalent (H1N1 only) influenza vaccine and seasonal influenza vaccine (H1N1, H3N2, and B-although we did not measure the antibody response to influenza B). We also evaluated antibody responses to the Pfizer mRNA-based COVID-19 vaccine.
We measured serum antibodies prior to vaccination and at two- or four-weeks post-immunization (COVID-19 vaccine recipients received the second dose three weeks after the first).
We evaluated the change in antibody response compared to pre-immunization levels, and we found that for all three vaccines, the change in antibody response to the vaccine was greater at four weeks post-immunization in participants who exercised for 90 minutes just after receiving the vaccine, compared to participants in the no exercise condition. In the seasonal flu vaccine study, we also evaluated 45-minutes of exercise post-immunization, but 45-minutes did not induce a significant increase in antibody compared to the no-exercise condition.
Participant allocations in the study:
Monovalent influenza vaccine
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Seasonal influenza vaccine
Pfizer–BioNTech COVID-19 vaccine
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MC: Can you talk about the type of antibody responses that you monitored and some of the key changes you quantified?
MH: We used an ELISA-based assay to measure IgG antibody responses specific to either the flu vaccine antigens or the COVID-19 vaccine spike RBD antigen. As these results are preliminary, we hope to follow up and measure long-term antibody responses to the COVID-19 vaccine (6-12 months post-immunization, and we would like to assess neutralizing antibodies as well).
MC: Are there other factors that could have contributed to the increased antibody response aside from exercise? How did you work to remove these confounding factors?
MH: With human studies with a limited number of participants, it is difficult to control for potential confounding factors, and so we cannot conclude from our limited findings that there were no confounding factors. We have more control over confounding factors in animal-based studies, and our experiments with mice also showed that 90-minutes of light to moderate intensity treadmill exercise improved antibody responses to an inactivated influenza vaccine (but not 45-minutes of exercise or 180-minutes of exercise). Yet we recognize that 90-minutes of exercise in a mouse may not represent 90-minutes of exercise in a human, so again further work is needed.
MC: Based on the evidence available so far you may not be able to direct people to exercise post-vaccination, but is there any harm if people would like to go and do that anyway?
MH: We have assessed the number and severity of reported side effects after flu vaccination or COVID-19 vaccination in our participants. We did not observe any significant difference in the number or severity of reported side effects comparing exercisers to non-exercisers, so from that perspective we are not aware of any harm, but of course longer-term follow-up (which is ongoing) can help us further address this question.
MC: From the data that you have available right now, what is the “take home” message?
MH: Based on our current evidence, the “take home message” is that if an individual regularly participates in exercise and can safely exercise at a light intensity for 90-minutes after immunization, there may be a benefit in terms of an increased antibody response to the vaccine. Future studies are needed to determine how or whether this change in antibody level may translate to enhanced protection.
MC: Can you talk about how you are advancing this research?
MH: If we are able to secure research funding, our objectives are to identify the mechanisms by which exercise may increase antibody responses, establish whether similar benefits are found on the T cell side of immunity (for mRNA-based COVID-19 vaccines), establish how long an exercise-induced increase in antibodies may persist post-immunization, determine whether neutralizing antibodies are enhanced, and define whether exercise has similar effects for COVID-19 booster immunization. Longer term work would address the extent to which immune alterations may translate to protection.
Professor Marian Kohut was speaking to Molly Campbell, Senior Science Writer for Technology Networks.