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The Influence of Trained Immunity in COVID-19 Vaccinated Individuals

NCT05705180 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 600

Last updated 2023-01-30

No results posted yet for this study

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, e.g. 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.

Conditions

  • Zoster Varicella
  • Vaccination; Infection

Interventions

BIOLOGICAL

recombinant adjuvanted zoster vaccine

vaccination with recombinant adjuvantes zoster vaccine

Sponsors & Collaborators

  • Wuerzburg University Hospital

    lead OTHER

Eligibility

Min Age
18 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2022-12-01
Primary Completion
2023-12-01
Completion
2024-12-01

Countries

  • Germany

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05705180 on ClinicalTrials.gov