Investigating COVID-19 Vaccine Immunity in Children in the Melbourne Infant Study of BCG for Allergy and Infection Reduction

Study Overview
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Brief Summary
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The COSI BAIR trial will involve approximately 60 children, aged 5 to 8 years old, comprising a subset of participants from the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial. The overall aim of this trial is to investigate the specific and heterologous effects of COVID-19 vaccination on immunity in children. COSI BAIR will aim to recruit its participants from the MIS BAIR Bacillus Calmette-Guérin (BCG)-naïve group. These children will be followed up until 28 days after their final Coronavirus Disease 2019 (COVID-19) vaccination. Venous blood samples will be collected at two study visits, at Murdoch Children's Research Institute (MCRI): Day 0 - baseline (day of COVID-19 vaccination #1), and Day 84 (28 days after COVID-19 vaccination #2).

Official Title
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A Single-arm Clinical Trial to Investigate COVID-19 Specific Vaccine and Heterologous Immunity in the Melbourne Infant Study of BCG for Allergy and Infection Reduction (COSI BAIR)

Conditions
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COVID-19, Vaccine Reaction, Immunization; Infection

Intervention / Treatment
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* Biological: Tozinameran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between five and eleven years (i.e. prior to the twelfth birthday) at the time of enrolment, Participant who was randomised in the MIS BAIR trial, and Was randomly allocated to receive and received BCG as part of the MIS BAIR trial, OR, Was randomly allocated to not receive and did not receive BCG; Is an individual whose parent/legally acceptable representative (LAR) consented to be contacted about future ethically approved research, during the MIS BAIR trial consent process, AND Has a parent/LAR capable of understanding the parent/LAR information statement and consent form (PICF) document and providing consent on the participant's behalf. Exclusion Criteria: Has a known hypersensitivity to the active ingredient or any of the excipients in tozinameran, Has a prior polymerase chain reaction (PCR)-confirmed diagnosis of COVID-19 whether symptomatic or not, Has received a COVID-19 vaccine (approved by the TGA or otherwise) prior to trial enrolment, An individual and/or parent/legally acceptable representative who is unwilling or unable to give written informed consent, An individual and/or parent/legally acceptable representative who is unwilling or unable to consent to attend all scheduled study visits, An individual and/or parent/LAR who is unwilling or unable to give consent for blood samples to be taken from the trial participant at each study visit, and Has or has had a clinically significant medical morbidity (e.g. immunocompromised because of congenital or acquired disorders or immunosuppressive medical treatment; a bleeding disorder; a recent history of inflammatory cardiac illness within the past 6 months, e.g., myocarditis, pericarditis, endocarditis, acute rheumatic fever (with active myocardial inflammation) or acute rheumatic heart disease, or acute decompensated heart failure), and Has received BCG at any other time than as part of the MIS BAIR trial.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: This trial is a non-controlled single-arm post-marketing exploratory trial where the approved COVID-19 vaccine will be used to determine whether COVID-19 vaccination alters heterologous (non-COVID-19-specific) immunity in children.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Approved COVID-19 vaccination<br>The approved COVID-19 vaccination arm will receive the COMIRNATY™ (tozinameran - BNT162b2 [mRNA]) COVID-19 VACCINE. The dose, strength of the dose unit, dosing interval and dosing period of tozinameran used in this trial will be as approved by the Therapeutic Goods Administration (TGA) and recommended by the Australian Technical Advisory Group on Immunisation (ATAGI) for children aged 5 to <12 years of age. The recommended dose of tozinameran for this age group is 10 µg (0.2 mL) and the recommended schedule is 2 doses, 8 weeks apart. Therefore two tozinameran doses of 10µg (0.2 mL) will be administered intramuscularly 8-weeks apart as part of this arm of the trial. | Biological: Tozinameran<br>* Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)<br>* Other names: Pfizer COVID-19 Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline of in vitro whole blood stimulation cytokine responses to COVID-19 specific and heterologous stimulants | The difference in cytokine concentrations between those measured on the day of first vaccination and 28 days after second vaccination is the primary outcome measure | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline of anti-SARS-CoV-2 antibody titres | The difference in anti-SARS-CoV-2 antibody titres between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 2 | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 
| Mean change from baseline of SARS-CoV-2-reactive T cell responses | The difference in SARS-CoV-2-reactive T cell responses, as measured by interferon-gamma producing units, between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 3 | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 
| Correlation of serological profiling of previous viral infections and antiviral responses, and post-vaccination anti-SARS-CoV-2 antibody titres | Pearson product-moment correlation coefficient of all trial participants' serological profiling of previous viral infections and antiviral responses on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 4. Previous viral infection organisms considered will include SARS-CoV-1, Middle East Respiratory Syndrome Coronavirus and circulating coronaviruses (eg. human coronavirus HKU1). | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 
| Correlation of serological profiling of vaccine-preventable disease antibody responses and post-vaccination anti-SARS-CoV-2 antibody titres | Pearson product-moment correlation coefficient of all trial participants' vaccine-preventable disease antibody responses on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 5. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles. | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 
| Correlation of whole blood cytokine responses to vaccine-preventable disease antigens and post-vaccination anti-SARS-CoV-2 antibody titres | Pearson product-moment correlation coefficient of all trial participants' whole blood cytokine responses to vaccine-preventable disease antigens on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 6. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles. | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 
| Mean change from baseline of vaccine-preventable disease antibody titres | The difference in vaccine-preventable disease antibody titres between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 7. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles. | Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-specific effects, COVID-19 vaccination, paediatric vaccination, heterologous immunity, mRNA vaccine