Biomarkers of Trained Immunity Following MMR Vaccination

NCT ID: NCT04646239

Last Updated: 2021-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

96 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-12-17

Study Completion Date

2021-06-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Covid19

Keywords

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COVID 19 Trained Immunity Infectious Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Heterologous stimuli

Intervention Type DIAGNOSTIC_TEST

In vitro exposure of peripheral blood mononuclear cells to heterologous stimuli

Neutralization assay

Intervention Type DIAGNOSTIC_TEST

In vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2

Interventions

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Heterologous stimuli

In vitro exposure of peripheral blood mononuclear cells to heterologous stimuli

Intervention Type DIAGNOSTIC_TEST

Neutralization assay

In vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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For example; RPMI medium, MMR, SARS-CoV-2, Influenza, TLR3 ligand, TLR7/8 ligand, TLR4 ligand

Eligibility Criteria

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Inclusion 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Michael Avidan

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael S Avidan, MD

Role: PRINCIPAL_INVESTIGATOR

Washington Univeristy School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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202011081

Identifier Type: -

Identifier Source: org_study_id