Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles

Abstract

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups—non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)—for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.

Effects of Exercise and Physical Activity Levels on Vaccination Efficacy: A Systematic Review and Meta-Analysis

“…Four RCTs [ 47 , 48 , 62 , 63 ] examined the effects of chronic aerobic exercise, and one RCT [ 64 ] investigated chronic physical activity levels. One CT [ 24 ] studied the effects of chronic involvement in taiji and qigong, one RCT [ 41 ], two CTs [ 27 , 39 ] the effects of chronic combined exercise (aerobic + resistance), and one CT [ 36 ] the effects of a nonspecific chronic exercise program. Finally, 16 CSS [ 23 , 29 , 32 , 33 , 37 , 40 , 51 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ] examined the relationship between physical activity levels and antibodies in response to various vaccines.…”

“…Most studies ( n = 29) [ 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 41 , 47 , 48 , 49 , 61 , 62 , 63 , 65 , 66 , 67 , 68 , 69 , 70 , 72 ] utilized influenza vaccines, six studies [ 34 , 40 , 45 , 50 , 51 , 64 ] pneumococcal, two SARS-CoV-2 [ 71 , 73 ], two tetanus [ 32 , 45 ], one human papillomavirus [ 60 ], one diphtheria [ 45 ], and one meningococcal vaccines [ 59 ]. The risk of bias assessment outcomes are shown in the Supplementary Materials (Table S2 and Figure S2) .…”

“…Regarding immediate symptomatic responses due to the administration of vaccines, 21 of the eligible studies that examined the effects of chronic exercise on vaccination efficacy and the associations of physical activity levels with vaccination efficacy reported no data [ 23 , 24 , 27 , 29 , 32 , 33 , 36 , 37 , 39 , 40 , 41 , 47 , 48 , 51 , 63 , 64 , 67 , 68 , 69 , 70 , 71 ]; one study reported no adverse effects [ 66 ], one study reported seven minor events [ 62 ], and one study reported 98.1% of local and 59.9% of systemic adverse effects in the 1st dose as well as 97.8% of local and 90.3% of systemic adverse effects in the 2nd dose [ 73 ]. Furthermore, out of the 24 eligible studies that examined the effects of chronic exercise on vaccination efficacy and the associations of physical activity levels with vaccination efficacy, two studies reported no changes in IL-10 [ 39 , 48 ], and one study reported reduced IL-10 after the intervention, which was associated with reduced cell immune responses [ 32 ]. Moreover, two studies reported no changes in IL-6 due to the intervention [ 39 , 69 ], and two studies reported no changes in C-reactive protein [ 37 , 73 ].…”

“…Furthermore, out of the 24 eligible studies that examined the effects of chronic exercise on vaccination efficacy and the associations of physical activity levels with vaccination efficacy, two studies reported no changes in IL-10 [ 39 , 48 ], and one study reported reduced IL-10 after the intervention, which was associated with reduced cell immune responses [ 32 ]. Moreover, two studies reported no changes in IL-6 due to the intervention [ 39 , 69 ], and two studies reported no changes in C-reactive protein [ 37 , 73 ]. These outcomes cannot form a clear picture of whether side effects and/or inflammatory responses played a role in vaccine responsiveness.…”

“…For 17 eligible studies [ 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], the means and SD s were depicted only in figures, as we were unable to retrieve data on the leading authors. Therefore, we used the WebPlotDigitizer 4.5, 2021, software (Rohatgi, USA) [ 42 ] to extract numerical data for our meta-analyses.…”