Ignite Creation Date:
2024-05-06 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 2:50 PM
Study NCT ID:
NCT05705180
Status:
RECRUITING
Last Update Posted:
2023-01-30
First Post:
2023-01-26
Brief Title:
The Influence of Trained Immunity in COVID-19 Vaccinated Individuals
Sponsor:
Wuerzburg University Hospital
Organization:
Wuerzburg University Hospital
Study Overview
Official Title:
The Influence of Trained Immunity in COVID-19 Vaccinated Individuals
Status:
RECRUITING
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The concept of trained immunity defines the long-term functional reprogramming of innate immune cells which is evoked by exogenous or endogenous insults and leads to an altered response towards a second challenge after return to a non-activated state and is characterized by several markers such as specific cytokines activation markers of innate immune cells and epigenetic modifications eg H3K4me3 Vaccinations have been shown to induce trained immunity and to have heterologous effects on other infections or vaccinations A recent article showed that individuals who had received recombinant adjuvanted zoster vaccine RZV before the pandemic had a 16 lower risk of COVID-19 diagnosis and a 32 lower risk of hospitalization suggesting a protective heterologous effect of RVZ on COVID19 infections So far the mechanisms behind these add-on benefits of RZV vaccination are on the hypothetical level and need further experimental evidence
Therefore we aim to investigate the specific humoral and cellular immune response towards COVID-19 vaccine in healthy individuals who were exposed to RZV 1 to 12 months before COVID-19 vaccination compared to individuals who did not receive RZV before Particular emphasis is layed on COVID-19 vaccine non-responders and individuals with breakthrough infections indicating lower vaccine efficacy compared to those who had no breakthrough infection
The primary objective is the cytokine profile of spike protein-stimulated T NK and NKT cells Spike protein stimulated T NK and NKT cells are characterized by cell surface markers transcription factor expression chemokine receptor expression activation and proliferation markers and by their lineage-specific cytokine pattern CD14 monocytes are magnetically isolated and further characterized by cell-culture experiments imitating a training and resting period after stimulation Epigenetic modifications by methylation of CpG regions are assessed at promoter enhancer and regulatory gene regions of immune cell characteristic transcription factors by bisulfite conversion and pyrosequencing Chromatin immunoprecipitation and ChIP-seq will be performed for analysis H3K4me3 associated with trained immunity Humoral and cellular reactivity to spike protein is analyzed by adapted ELISA and neutralisation assays and by ELISpot and flow cytometry respectively and correlated
From our findings we expect to learn about the role of previous RZV on immunogenicity and efficacy of COVID-19 vaccination and whether mechanisms of trained immunity play a role for better responses towards COVID-19 vaccination
Therefore we aim to investigate the specific humoral and cellular immune response towards COVID-19 vaccine in healthy individuals who were exposed to RZV 1 to 12 months before COVID-19 vaccination compared to individuals who did not receive RZV before Particular emphasis is layed on COVID-19 vaccine non-responders and individuals with breakthrough infections indicating lower vaccine efficacy compared to those who had no breakthrough infection
The primary objective is the cytokine profile of spike protein-stimulated T NK and NKT cells Spike protein stimulated T NK and NKT cells are characterized by cell surface markers transcription factor expression chemokine receptor expression activation and proliferation markers and by their lineage-specific cytokine pattern CD14 monocytes are magnetically isolated and further characterized by cell-culture experiments imitating a training and resting period after stimulation Epigenetic modifications by methylation of CpG regions are assessed at promoter enhancer and regulatory gene regions of immune cell characteristic transcription factors by bisulfite conversion and pyrosequencing Chromatin immunoprecipitation and ChIP-seq will be performed for analysis H3K4me3 associated with trained immunity Humoral and cellular reactivity to spike protein is analyzed by adapted ELISA and neutralisation assays and by ELISpot and flow cytometry respectively and correlated
From our findings we expect to learn about the role of previous RZV on immunogenicity and efficacy of COVID-19 vaccination and whether mechanisms of trained immunity play a role for better responses towards COVID-19 vaccination
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None