Distinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly
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ABSTRACT:
PROVIDER: PRJEB56539 | ENA |
REPOSITORIES: ENA
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Project description:Seasonal influenza outbreaks, especially in high-risk groups such as the elderly, represent an important public health problem. Prevailing inadequate efficacy of seasonal vaccines is a crucial bottleneck. Understanding the immunological and molecular mechanisms underpinning differential influenza vaccine responsiveness is essential to improve vaccination strategies. Here we show comprehensive characterization of the immune response of randomly selected elderly participants (≥ 65 years), immunized with the adjuvanted influenza vaccine Fluad. In-depth analyses by serology, multi-parametric flow cytometry, multiplex and transcriptome analysis, coupled to bioinformatics and mathematical modelling, reveal distinguishing immunological and molecular features between responders and non-responders defined by vaccine-induced seroconversion. Non-responders are specifically characterized by multiple suppressive immune mechanisms. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness independently of confounding age-related effects, with the potential to facilitate development of tailored vaccination strategies for the elderly.
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Project description:The significant economic burden and high mortality rates resulting from seasonal influenza outbreaks, especially in high risk groups such as the elderly, represent an important public health problem. The prevailing inadequate efficacy of seasonal vaccines, both conventional and elderly-tailored, is a crucial bottleneck. Consequentially, understanding immunological and molecular mechanisms resulting in differential influenza vaccine responsiveness is a prerequisite for the development of new or improved vaccination strategies. To assess differences within the specific risk group of the elderly, randomly selected individuals (≥ 65 years) were immunized with the adjuvanted influenza vaccine Fluad®. Samples were subjected to transcriptome analysis. The analyses revealed profound features segregating vaccine responders from nonresponders as classified according to their vaccine-induced sero-conversion. Non-responders are characterized by a poorly functional, suppressive phenotype, showing a weaker humoral and cellular immune activation and more suppressive regulatory T and B cells. Triple responders display an efficient immune functionality characterized by the activation of humoral and cellular immunity and the up-regulation of genes related to signaling pathways, including those for anti-viral responses, protein processing and B cell activation. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness regardless of confounding age-dependent effects.
2022-09-29 | GSE211368 | GEO
Project description:The significant economic burden and high mortality rates resulting from seasonal influenza outbreaks, especially in high risk groups such as the elderly, represent an important public health problem. The prevailing inadequate efficacy of seasonal vaccines, both conventional and elderly-tailored, is a crucial bottleneck. Consequentially, understanding immunological and molecular mechanisms resulting in differential influenza vaccine responsiveness is a prerequisite for the development of new or improved vaccination strategies. To assess differences within the specific risk group of the elderly, randomly selected individuals (≥ 65 years) were immunized with the adjuvanted influenza vaccine Fluad®. Samples were subjected to single cell transcriptome analysis. The analyses revealed profound features segregating vaccine responders from nonresponders as classified according to their vaccine-induced sero-conversion. Non-responders are characterized by a poorly functional, suppressive phenotype, showing a weaker humoral and cellular immune activation and more suppressive regulatory T and B cells. Triple responders display an efficient immune functionality characterized by the activation of humoral and cellular immunity and the up-regulation of genes related to signaling pathways, including those for anti-viral responses, protein processing and B cell activation. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness regardless of confounding age-dependent effects.
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Project description:Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients.
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2021-05-17 | E-MTAB-10309 | biostudies-arrayexpress
Project description:Distinct immunological and molecular signatures predict influenza vaccine responsiveness in the elderly
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Project description:Distinct immunological and molecular signatures predict influenza vaccine responsiveness in the elderly (scRNA Seq)
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Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2008 influenza season, healthy adults were vaccinated with LAIV (28 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
2011-07-10 | E-GEOD-29615 | biostudies-arrayexpress
Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2008 influenza season, healthy adults were vaccinated with TIV (28 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
2011-07-10 | E-GEOD-29617 | biostudies-arrayexpress
Project description:Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans, and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. During the 2007 Influenza season, healthy adults were vaccinated with TIV (9 vaccinees), and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
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