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Search: WFRF:(Müller Mira)

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2.
  • Gao, Yu, et al. (author)
  • Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
  • 2022
  • In: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 55:9, s. 1732-1746.e5
  • Journal article (peer-reviewed)abstract
    • Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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3.
  • Grooten, Wilhelmus Johannes Andreas, et al. (author)
  • Health risk appraisals in Swedish occupational health services
  • 2016
  • In: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 55:4, s. 849-859
  • Journal article (peer-reviewed)abstract
    • Background: Health risk appraisals (HRAs) in occupational health services (OHS) in Sweden are very commonly used for health promotion issues, but not much research has explored the extent and nature of individual feedback that is provided.Objectives: This study aimed to describe and explore HRAs in OHS regarding the content of the feedback in relation to the individual status and overall employee satisfaction.Methods: Feedback (evaluation and advice) and employee satisfaction with HRA were studied in employees that participated in health risk appraisals with a specific feedback session (HRA-F) (n = 272) and employees that participated in a single session (HRA-S) (n = 104). Associations between feedback and individual status concerning life style were assessed with Cohen's kappa (k).Results: The employees received mainly information and advice for improvement on health and lifestyle issues (89-100%), while advice for improvement of working conditions was less common (15-59%). The feedback provided on life style was not based on individual status (k < 0.4), except for smoking and risky alcohol consumption (k > 0.55). A great majority of employees reported good overall satisfaction with their HRAs.Conclusions: The evaluation and feedback given to employees after HRAs should be based more on HRA-results and advice could be focused more on work-related factors.
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4.
  • Grooten, Wilhelmus Johannes Andreas, et al. (author)
  • Non-participation in initial and repeated health risk appraisals : a drop-out analysis based on a health project
  • 2019
  • In: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 19:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Health risk assessment (HRAs) are commonly used by occupational health services (OHS) to aid workplaces in keeping their employees healthy, but for unknown reasons, many employees choose not to participate in the HRAs. The aim of the study was to explore whether demographic, lifestyle and health-related factors in employees are associated with non-participation in initial and repeated HRAs.METHODS: In an OHS-based health project, 2022 municipal employees were asked to participate in three repeated HRAs. Multiple logistic regression analyses were used so as to determine associations between non-participating and demographic, lifestyle and health-related factors (e.g. biomarkers).RESULTS: Among the employees who were asked to participate in the health project, more than half did not participate in any HRA and among those who did, more than one third did not participate in repeated HRAs. Young age, male sex and being employed in the Technical department or Health and Social Care department in comparison with being employed in the department for Childcare and Education were factors significantly associated with non-participation in the initial HRA. These factors, together with being on sick leave and having unhealthy dietary habits, were factors associated with non-participation in repeated HRAs.CONCLUSIONS: Among the non-participators in initial HRAs and in repeated HRAs younger men and those already related to ill-health were overrepresented. This implicates that health care providers to a higher extent should focus on "those most needed" and that employers should be more engaged in results of repeated HRA's. Future studies should focus on modifiable variables that could make the HRAs more attractive and inclusive.
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5.
  • Müller, Thomas R., et al. (author)
  • Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states
  • 2023
  • In: Science Translational Medicine. - 1946-6234 .- 1946-6242. ; 15:704, s. eadg9452-
  • Journal article (peer-reviewed)abstract
    • Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA+ effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
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6.
  • Müller, Thomas R., et al. (author)
  • Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant
  • 2024
  • In: Cell Host and Microbe. - : Elsevier. - 1931-3128 .- 1934-6069. ; 32:2, s. 156-161.e3
  • Journal article (peer-reviewed)abstract
    • T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.
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