Zoster VaricellaNCT05705180
The Influence of Trained Immunity in COVID-19 Vaccinated Individuals
An observational study of Zoster Varicella and Vaccination; Infection, run by Wuerzburg University Hospital at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Zoster Varicella, Vaccination; Infection
- What is being tested?
- recombinant adjuvanted zoster vaccine
- Type of treatment
- Vaccines
- How many people
- 600 participants
- Where
- 1 siteGermany
- Study dates
- 1 Dec 2022to 1 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Immunologically healthy individuals who were vaccinated at least twice with COVID-19 mRNA vaccine (either Comirnaty or Moderna) are taken from CoVaKo study cohort (Group A). Immunologically healthy is defined at inclusion by normal leucocyte and lymphocyte counts, normal CRP and ESR according to age range, no severe allergies requiring daily therapy, no congenital or acquired immunodeficiency or immunosuppression. A control group (Group B) consists of individuals who did not receive RZV 1-12 months before COVID-19 vaccination.
Who may be able to join
- Group 1, retrospective (samples already stored, CoVaKo study cohort): healthy (n=420) Group 2, prospective (samples to be recruited, CoVaKo study cohort): healthy (n=180)
- Age 18-90 years, stratified into <60 and ≥60 years
- at least 2 COVID-19-mRNA vaccinations as equivalent to primary immunization and the third and/or fourth dose considered as booster, as recommended for all individuals >12 years (third dose) and for risk groups, medical staff, nursing home residents (fourth dose) in Germany Only individuals naive for SARS-CoV-2 (negative N-specific and S-specific-IgG antibody status, no history of PCR+ swab) before COVID-19 vaccination will be included.
Who cannot join
- High-dose glucocorticoids >10 mg/day
- Immunosuppressive therapy
- Biologics or immunomodulators
- Transplantation
- Cancer
- Autoimmunity
Show all 9Show fewer
- RZV after COVID-19 vaccination
- COVID-19 PCR+ before COVID-19 vaccination
- Other types of COVID-19 vaccines than mRNA vaccines
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Wuerzburg
Würzburg, Bavaria, 97080
Martina Prelog, Prof. Dr., 093120127708, Prelog_M@ukw.de
About this study
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.
Read more
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
- Being tested
- recombinant adjuvanted zoster vaccine
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant adjuvanted zoster vaccineBiological
vaccination with recombinant adjuvantes zoster vaccine
| Study group | Role | What they receive |
|---|---|---|
| A Retrospective samples | Retrospective (samples already stored, CoVaKo study cohort): Retrospective samples were consecutively collected during March 2020 and March 2022 (n=420).
Group 1A: RZV 1-12 months before COVID-19 -mRNA vaccination Group 1B: no RZV (control arm) Receives: Biological: recombinant adjuvanted zoster vaccine | |
| B Prospective samples | Prospective (samples to be recruited, CoVaKo study cohort): Prospective samples will be collected April 2022 to July 2022 (n=180).
Group 2A: RZV 1-12 months before COVID-19 -mRNA vaccination Group 2B: no RZV (control arm) Receives: Biological: recombinant adjuvanted zoster vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interferon-gamma
Spot forming units in Interferon-gamma ELISpot assay
Measured: 12 months
Secondary outcomes (2)
Spike-specific IgG antibodies
Spike-specific IgG antibodies measured in BAU/ml
Measured: 12 months
Spike-specific IgG antibody avidity
Spike-specific IgG antibody avidity measured in relative avidity by adapted ELISA
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start1 Dec 2022
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Zoster VaricellaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Martina Prelog, Wuerzburg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705180
- Sponsor's protocol ID
- 10.940-3.22_VXSS-218827
- Status last verified
- Jan 2023
- First submitted
- 26 Jan 2023
- Last updated
- 30 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Trained Immunity in COVID-19 Vaccinated Individuals
- ClinicalTrials.gov ID
- NCT05705180
- Acronym / sponsor ID
- 10.940-3.22_VXSS-218827
- Conditions
- Zoster Varicella, Vaccination; Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A Retrospective samples | – | Biological: recombinant adjuvanted zoster vaccineRetrospective (samples already stored, CoVaKo study cohort): Retrospective samples were consecutively collected during March 2020 and March 2022 (n=420). Group 1A: RZV 1-12 months before COVID-19 -mRNA vaccination Group 1B: no RZV (control arm) |
| B Prospective samples | – | Biological: recombinant adjuvanted zoster vaccineProspective (samples to be recruited, CoVaKo study cohort): Prospective samples will be collected April 2022 to July 2022 (n=180). Group 2A: RZV 1-12 months before COVID-19 -mRNA vaccination Group 2B: no RZV (control arm) |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Immunologically healthy individuals who were vaccinated at least twice with COVID-19 mRNA vaccine (either Comirnaty or Moderna) are taken from CoVaKo study cohort (Group A). Immunologically healthy is defined at inclusion by normal leucocyte and lymphocyte counts, normal CRP and ESR according to age range, no severe allergies requiring daily therapy, no congenital or acquired immunodeficiency or immunosuppression. A control group (Group B) consists of individuals who did not receive RZV 1-12 months before COVID-19 vaccination.
Key inclusion criteria (3 listed)
- Group 1, retrospective (samples already stored, CoVaKo study cohort): healthy (n=420) Group 2, prospective (samples to be recruited, CoVaKo study cohort): healthy (n=180)
- Age 18-90 years, stratified into <60 and ≥60 years
- at least 2 COVID-19-mRNA vaccinations as equivalent to primary immunization and the third and/or fourth dose considered as booster, as recommended for all individuals >12 years (third dose) and for risk groups, medical staff, nursing home residents (fourth dose) in Germany Only individuals naive for SARS-CoV-2 (negative N-specific and S-specific-IgG antibody status, no history of PCR+ swab) before COVID-19 vaccination will be included.
Key exclusion criteria (9 listed)
- High-dose glucocorticoids >10 mg/day
- Immunosuppressive therapy
- Biologics or immunomodulators
- Transplantation
- Cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant adjuvanted zoster vaccinevaccination with recombinant adjuvantes zoster vaccine | Biological | A Retrospective samples, B Prospective samples |
Primary outcome
Interferon-gamma
Time frame: 12 months
Spot forming units in Interferon-gamma ELISpot assay
2 secondary outcomes
Spike-specific IgG antibodies
Time frame: 12 months
Spike-specific IgG antibody avidity
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Zoster Varicella and Vaccination; Infection, run by Wuerzburg University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martina Prelog, Prof. Dr. (093120127708, Prelog_M@ukw.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interferon-gamma (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.