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Biomarkers of Trained Immunity Following MMR Vaccination

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ClinicalTrials.gov Identifier: NCT04646239
Recruitment Status : Active, not recruiting
First Posted : November 27, 2020
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
Michael Avidan, Washington University School of Medicine

Study Description
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Brief Summary:

This is a substudy of NCT04333732. The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially viral associated products, in the MMR vaccinated compared placebo groups.

All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.


Condition or disease Intervention/treatment
Covid19 Diagnostic Test: Heterologous stimuli Diagnostic Test: Neutralization assay

Detailed Description:

A sub-study of the CROWN CORONATION Trial (COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION; NCT04333732). The goal of this sub-study is to identify and characterize biomarkers of trained immunity by measuring, in vitro, immune responses to heterologous products, especially virally associated products, in those exposed to MMR vaccine injection compared to those exposed to 0.9% sodium chloride ('normal saline') placebo injection.

A secondary objective is comparison of SARS-CoV-2 neutralization assays between MMR and placebo comparison groups around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection.

All participants are randomly assigned to MMR or placebo injection at baseline, followed by SARS-CoV-2 specific vaccination. Blood is drawn around 60 to 90 days after the last SARS-CoV-2 specific vaccine injection. Peripheral blood mononuclear cells (PMBC) will be isolated from samples and stimulated with heterologous products (for example; Roswell Park Memorial Institute medium [RPMI; negative control], MMR [the vaccine itself as specific stimulus], severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2; heat inactivated], influenza virus [heat inactivated], toll-like receptor 3 ligand [TLR3 ligand; poly I:C], toll-like receptor 7/8 ligand [TLR7/8 ligand; R848], toll-like receptor 4 ligand [TLR4 ligand; lipopolysaccharide (LPS)]). Supernatants will be assayed by multiplex luminex protein assay at 24 hr (for example; type I interferons [IFN], interleukin [IL]-1β , IL-6, tumor necrosis factor [TNF]-α) and after 5 days (for example; IFN-γ, IL-17, IL-22, IL-10). This process of testing stimulus-response will be conducted on both the baseline and day 30 samples, collected from both the MMR and Placebo groups.

Neutralization assay will be conducted on all samples using wild-type SARS-CoV-2.

Measles IgG titres will be measured on all samples. Measles IgG titres will be used for sensitivity analysis.

Study Design
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Study Type : Observational
Actual Enrollment : 96 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Determining Biomarkers of Trained Immunity in a Randomized Controlled Trial of the Measles, Mumps, and Rubella Vaccine - a Sub-study of the CROWN CORONATION Trial
Actual Study Start Date : December 17, 2020
Actual Primary Completion Date : June 28, 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Participants in the CROWN CORONATION trial
The CROWN CORONATION trial will randomly allocate adult participants to a single intramuscular injection of MMR vaccine or Placebo (0.9% saline). All participants in this sub-study receive SARS-CoV-2 specific vaccine subsequent to the MMR or Placebo injection.
 Diagnostic Test: Heterologous stimuli
In vitro exposure of peripheral blood mononuclear cells to heterologous stimuli
Other Name: For example; RPMI medium, MMR, SARS-CoV-2, Influenza, TLR3 ligand, TLR7/8 ligand, TLR4 ligand

Diagnostic Test: Neutralization assay
In vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2


Outcome Measures
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Primary Outcome Measures :
  1. Cytokine (or chemokine) production in response to heterologous stimuli [ Time Frame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection ]
    Cytokines such as TNF-α, IL-1β and IL-6 produced by human monocytes, and IFN-γ produced by natural killer (NK)-cells, are markers of trained immunity and these (and other cytokines and chemokines) will be measured in supernatants of stimulated PBMCs from a cohort of participants in the CROWN CORONATION trial. All cytokines and chemokines are measured in picograms/milliliter.


Secondary Outcome Measures :
  1. Neutralization assay [ Time Frame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection ]
    Neutralizing antibody activity to wild-type SARS-CoV-2


Biospecimen Retention:   Samples With DNA
45 mL peripheral blood drawn around 60 to 90 days after last SARS-CoV-2 vaccine injection. De-identified plasma and peripheral blood mononuclear cells will be extracted from the collected specimens and stored for analysis.

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
The CROWN CORONATION trial enrolls adults at risk of developing COVID-19 due to their work in the healthcare environment. To be eligible, prospective participants for the CROWN CORONATION trial must not have a contra-indication to receiving the live attenuated Measles, Mumps and Rubella vaccine (MMR) and must not be exposed to agents that may complicate the interpretation of findings regarding the hypothesized protective effect of MMR for the prevention of COVID-19. The sub-study will consecutively approach all participants enrolled in the CROWN CORONATION trial to elicit enrolment in the sub-study cohort.
Criteria

Inclusion/ Exclusion Criteria:

Prospective participant must already be enrolled into the CROWN CORONATION trial at the sub-study location. Refer to NCT04333732 for list of inclusion / exclusion criteria for the study population.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04646239


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Michael S Avidan, MD Washington Univeristy School of Medicine
More Information
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Responsible Party: Michael Avidan, Professor, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04646239    
Other Study ID Numbers: 202011081
First Posted: November 27, 2020    Key Record Dates
Last Update Posted: July 21, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The project team will make the de-identified data available to the public within 1 year after publication using a public repository. Prior to that time, data will be deposited in the Washington University Open Scholarship repository. Any request for data not deposited in the repository must be directed to the Principal Investigator
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: 1 Year

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Avidan, Washington University School of Medicine:
COVID 19
Trained Immunity
Infectious Diseases