NCT04646239

Biomarkers of Trained Immunity Following MMR Vaccination

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 96 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

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.

Conditions

• Covid19

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Heterologous stimuli	In vitro exposure of peripheral blood mononuclear cells to heterologous stimuli
DIAGNOSTIC_TEST	Neutralization assay	In vitro measurement of neutralizing antibody activity to wild-type SARS-CoV-2

Timeline

• Start date: 2020-12-17
• Primary completion: 2021-06-28
• Completion: 2021-06-28
• First posted: 2020-11-27
• Last updated: 2021-11-26

Locations

1 site across 1 country: United States