scholarly journals No Effect of Acute Eccentric Resistance Exercise on Immune Responses to Influenza Vaccination in Older Adults: A Randomized Control Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud T. Elzayat ◽  
Melissa M. Markofski ◽  
Richard J. Simpson ◽  
Mitzi Laughlin ◽  
Emily C. LaVoy

IntroductionOlder adults are at elevated risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response.PurposeCompare antibody and cell mediated immune responses to influenza vaccination in older adults who performed eccentric resistance exercise immediately prior to vaccination to those who did not exercise.MethodsTwenty nine resistance training-naive older adults (20 women, 73.9 ± 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-Op), and seated rest (No-Ex). Exercise consisted of 10 sets of 5 eccentric unilateral repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all received the 2018 quadrivalent influenza vaccine (Seqirus Afluria) in the non-dominant deltoid. Antibody titers against each influenza vaccine strain were determined by hemagglutinin inhibition assays at baseline, 6-, and 24-weeks post-vaccination. Influenza-specific T cells were quantified after stimulation with the vaccine by intracellular cytokine staining.ResultsNo significant group x time effects were found in antibody responses to any strain (interaction for A/H1N1: p = 0.682; A/H3N2: p = 0.644; B/Colorado/06/2017: p = 0.262; B/Phuket/3073/2013: p = 0.851). Groups did not differ in fold-increase of antibody titers 6- and 24-weeks post-vaccination. Influenza-specific T-cells did not differ between groups at any time (comparison at baseline: p = 0.985; 6-weeks: p = 0.889; 24 weeks: p = 0.857). One subject (Ex-S) reported flu-like symptoms 18 weeks post-vaccination.ConclusionAcute arm eccentric exercise did not influence antibody titers or cell mediated immune responses to the influenza vaccine delivered post-exercise in older adults. More strenuous exercise may be required for exercise to act as an adjuvant. ClinicalTrials.gov Identifier: NCT03736759.

2020 ◽  
Author(s):  
Mahmoud T Elzayat ◽  
Melissa M Markofski ◽  
Richard J Simpson ◽  
Mitzi Laughlin ◽  
Emily C LaVoy

Older adults are at elevated risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As acute eccentric resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response. PURPOSE: Compare antibody responses to influenza vaccination in older adults who performed resistance exercise prior to vaccination to those who did not exercise. METHODS: 29 resistance training-naive older adults (20 women, 73.9 +/- 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-OP), and seated rest (No-Ex). Exercise was unilateral and consisted of 10 sets of 5 eccentric repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all subjects received the 2018 quadrivalent influenza vaccine (Seqirus Afluria) in the non-dominant deltoid. Antibody titers against the four influenza vaccine strains were determined by hemagglutinin inhibition assays at baseline, 6-, and 24-weeks post-vaccination. Group differences in antibody titers by time were assessed by restricted maximum likelihood mixed models. Fold-changes in antibody titers 6- and 24-weeks from baseline were compared between groups by Kruskal-Wallis tests. RESULTS: No significant group x time effects were found for any strain. Groups did not differ in fold-increase of antibody titers 6- and 24-weeks post-vaccination. Although seroconversion rates remained low, only one subject (Ex-S) reported flu-like symptoms 18 weeks post-vaccination. CONCLUSION: Acute arm eccentric exercise did not influence antibody titers to the influenza vaccine delivered post-exercise in older adults. More strenuous exercise may be required for exercise to act as an adjuvant.


2021 ◽  
Vol 2 ◽  
Author(s):  
Chris P. Verschoor ◽  
Laura Haynes ◽  
Graham Pawelec ◽  
Mark Loeb ◽  
Melissa K. Andrew ◽  
...  

Background: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that granzyme B (GrB) activity in influenza A/H3N2 challenged peripheral blood mononuclear cells (PBMC) correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection.Methods: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n = 582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20–40 years, n = 79) received SD-SVV. At 0, 4, 10, and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, and in older adults, we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose.Results: Prior to vaccination, younger compared to older adults produced significantly higher IFNγ, IL-10, and iGrB levels. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups; all three groups showed a significant iGrB response to vaccination. In a regression analysis, frailty was associated with lower IFNγ levels, whereas female sex and HD-SVV with higher IL-10 levels. Age and SD-SVV were associated with lower iGrB levels. The effect of prior season influenza vaccination was decreased iGrB levels, and increased IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers.Conclusion: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.Clinical Trial Registration: ClinicalTrials.gov (NCT02297542).


2019 ◽  
Vol 221 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Tiffany W Y Ng ◽  
Ranawaka A P M Perera ◽  
Vicky J Fang ◽  
Emily M Yau ◽  
J S Malik Peiris ◽  
...  

Abstract Background Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same. Methods An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015–2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160. Results Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160. Conclusions Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kelly Huang ◽  
Shu-Wen Lin ◽  
Wang-Huei Sheng ◽  
Chi-Chuan Wang

AbstractThe coronavirus disease of 2019 (COVID-19) has caused a global pandemic and led to nearly three million deaths globally. As of April 2021, there are still many countries that do not have COVID-19 vaccines. Before the COVID-19 vaccines were developed, some evidence suggested that an influenza vaccine may stimulate nonspecific immune responses that reduce the risk of COVID-19 infection or the severity of COVID-19 illness after infection. This study evaluated the association between influenza vaccination and the risk of COVID-19 infection. We conducted a retrospective cross-sectional study with data from July 1, 2019, to June 30, 2020 with the Claims data from Symphony Health database. The study population was adults age 65 years old or older who received influenza vaccination between September 1 and December 31 of 2019. The main outcomes and measures were odds of COVID-19 infection and severe COVID-19 illness after January 15, 2020. We found the adjusted odds ratio (aOR) of COVID-19 infection risk between the influenza-vaccination group and no-influenza-vaccination group was 0.76 (95% confidence interval (CI), 0.75–0.77). Among COVID-19 patients, the aOR of developing severe COVID-19 illness was 0.72 (95% CI, 0.68–0.76) between the influenza-vaccination group and the no-influenza-vaccination group. When the influenza-vaccination group and the other-vaccination group were compared, the aOR of COVID-19 infection was 0.95 (95% CI, 0.93–0.97), and the aOR of developing a severe COVID-19 illness was 0.95 (95% CI, 0.80–1.13). The influenza vaccine may marginally protect people from COVID-19 infection.


2021 ◽  
Vol 12 ◽  
Author(s):  
Eduardo S. Felismino ◽  
Juliana M. B. Santos ◽  
Marcelo Rossi ◽  
Carlos A. F. Santos ◽  
Edison L. Durigon ◽  
...  

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.


2008 ◽  
Vol 15 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Giulia Freer ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
Francesca Tarabella ◽  
Valentina Catalucci ◽  
...  

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.


2019 ◽  
Vol 7 ◽  
pp. 251513551987467
Author(s):  
Georgia Koutsoumpli ◽  
Peng Peng Ip ◽  
Ilona Schepel ◽  
Baukje Nynke Hoogeboom ◽  
Annemarie Boerma ◽  
...  

Background: Antigen-specific T cell immune responses play a pivotal role in resolving acute and chronic hepatitis C virus (HCV) infections. Currently, no prophylactic or therapeutic vaccines against HCV are available. We previously demonstrated the preclinical potency of therapeutic HCV vaccines based on recombinant Semliki Forest virus (SFV) replicon particles. However, clinical trials do not always meet the high expectations of preclinical studies, thus, optimization of vaccine strategies is crucial. In efforts to further increase the frequency of HCV-specific immune responses in the candidate SFV-based vaccines, the authors assessed whether inclusion of three strong, so-called universal helper T cell epitopes, and an endoplasmic reticulum localization, and retention signal (collectively termed sigHELP-KDEL cassette) could enhance HCV-specific immune responses. Methods: We included the sigHELP-KDEL cassette in two of the candidate SFV-based HCV vaccines, targeting NS3/4A and NS5A/B proteins. We characterized the new constructs in vitro for the expression and stability of the transgene-encoded proteins. Their immune efficacy with respect to HCV-specific immune responses in vivo was compared with the parental SFV vaccine expressing the corresponding HCV antigen. Further characterization of the functionality of the HCV-specific CD8+ T cells was assessed by surface and intracellular cytokine staining and flow cytometry analysis. Results: Moderate, but significantly, enhanced frequencies of antigen-specific immune responses were achieved upon lower/suboptimal dosage immunization. In optimal dosage immunization, the inclusion of the cassette did not further increase the frequencies of HCV-specific CD8+ T cells when compared with the parental vaccines and the frequencies of effector and memory populations were identical. Conclusion: We hypothesize that the additional effect of the sigHELP-KDEL cassette in SFV-based vaccines depends on the immunogenicity, nature, and stability of the target antigen expressed by the vaccine.


2020 ◽  
Vol 12 (564) ◽  
pp. eabd5487 ◽  
Author(s):  
Carl A. Pierce ◽  
Paula Preston-Hurlburt ◽  
Yile Dai ◽  
Clare Burn Aschner ◽  
Natalia Cheshenko ◽  
...  

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor–α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.


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