Similar Datasets
Project description:Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses.
2024-01-29 | GSE246937 | GEO
Project description:Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses.
2024-01-29 | GSE246525 | GEO
Project description:Systems biology analysis reveals distinct molecular signatures promoting immune responsiveness to the BNT162b COVID-19 vaccine
| PRJNA1035124 | ENA
Project description:Systems biology analysis reveals distinct molecular signatures promoting immune responsiveness to the BNT162b COVID-19 vaccine [scRNA-seq]
| PRJNA1035131 | ENA
Project description:Systems biology analysis reveals distinct molecular signatures promoting immune responsiveness to the BNT162b COVID-19 vaccine [bulk RNA-seq]
| PRJNA1033573 | ENA
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.
| S-EPMC9653450 | biostudies-literature
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.
2022-09-29 | GSE211560 | GEO
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
2022-10-14 | PXD031969 | Pride
Project description:This project is an applied clinical study aimed at analyzing different patterns in responder and non-responder following influenza vaccination.
| PRJEB56539 | ENA