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.
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.
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
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.
Washington University School of Medicine
Saint Louis, Missouri, United States
Michael S Avidan, MD, Principal Investigator
Washington Univeristy School of Medicine