Clinical trial NCT04646239: Biomarkers of Trained Immunity Following MMR Vaccination
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Keywords: COVID 19
Trained Immunity
Infectious Diseases
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-11-27
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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.

Primary outcomes:
measure: Cytokine (or chemokine) production in response to heterologous stimuli
timeFrame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
Secondary outcomes:
measure: Neutralization assay
timeFrame: Around 60 to 90 days after last SARS-CoV-2 specific vaccine injection
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington Univeristy School of Medicine
name: Michael S Avidan, MD
role: PRINCIPAL_INVESTIGATOR
References: