Covid-19 Vaccination in Adolescents and Children

Study Overview
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Brief Summary
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Objectives To assess the reactogenicity, measure the adaptive immune responses and track the long-term immune memory in healthy children and adults as well as pediatric patients receiving the COVID-19 vaccines-BNT162b2, CoronaVac-chosen by the Hong Kong Government; to compare the reactogenicity and immunogenicity across the vaccines used for these children and adults. Hypothesis to be tested The safety profile and the magnitude and durability of immune responses to the COVID-19 vaccines in children are non-inferior to those in adults. Design and subjects A single-site, comparative nonrandomised clinical trial for 450 healthy individuals or patients under 18 years old and one or both healthy parents and unrelated adults to receive one of COVID-19 vaccines by intramuscular injection (and intradermal injection) Instruments Mobile app for subjects to record adverse effects, enzyme-linked immunosorbent assay, plaque reduction neutralization assay, luciferase immunoprecipitation system assay and flow cytometry. Interventions BNT162b2 and CoronaVac, by intramuscular or intradermal route Main outcome measures Types and frequencies of adverse effects within 7 days, and changes and peaks of antibody levels and antigen-specific memory T cell responses for 3 years.

Official Title
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To Compare the Reactogenicity and Immunogenicity of Recommended COVID-19 Vaccines in Young Adolescents and Children in Hong Kong

Conditions
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Covid19

Intervention / Treatment
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* Biological: Tozinameran
* Biological: CoronaVac
* Biological: CoronaVac, intradermal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent from the parents or a legally acceptable representative for an underage participant biological parents of students enrolled in the trial or unrelated healthy adults ability to adhere to the follow-up schedules willingness to report reactogenicity daily for 7 days post dose 1, 2 and 3 (and 4) proactively willingness to receive that vaccine available for that particular recruitment period (as student-parent pair, if applicable) good past health, including pre-existing clinically stable disease, such as paediatric or immune disorders prior COVID-19 (for COVID-19 survivor subgroup) Exclusion Criteria: 1. reported pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 100 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BNT162b2 (adult/adolescent)<br>BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (or intradermal for immunocompromised patients; or by graded challenge with history of non-severe allergy to PEG-containing drugs) 30ug/0.3ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19 | Biological: Tozinameran<br>* mRNA vaccine developed by BioNTech against COVID-19<br>* Other names: BNT162b2;|
| Experimental: CoronaVac (intramuscular)<br>CoronaVac by SinoVac Intramuscular injection 3ug/0.5ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19 | Biological: CoronaVac<br>* Inactivated virus vaccine developed by SinoVac against COVID-19, intramuscular<br>|
| Experimental: CoronaVac (intradermal)<br>CoronaVac by SinoVac Intradermal injection 3ug/0.5ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19 | Biological: CoronaVac, intradermal<br>* Inactivated virus vaccine developed by SinoVac against COVID-19, intradermal<br>|
| Experimental: BNT162b2 (paediatric)<br>BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (for immunocompromised patients only) 10ug/0.1ml per dose 4 doses for immunocompromised patients | Biological: Tozinameran<br>* mRNA vaccine developed by BioNTech against COVID-19<br>* Other names: BNT162b2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions | Percentage of occurrence, types, duration and severity of adverse reactions occurring within 7 days | 7 days post-doses 1, 2 and 3 (and 4) | 
| Binding antibody response | Geometric mean levels of SARS-CoV2 S and S-RBD-specific binding antibody and related markers as determined by Enzyme-linked Immunosorbent Assay | 1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4) | 
| Neutralizing antibody response | Geometric mean levels and geometric mean fold rise of SARS-CoV2 neutralizing antibodies as determined by plaque reduction neutralization assay and surrogate assays | 1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4) | 
| T cell response | Geometric mean percentage of CD4 and CD8 T cells specific to SARS-CoV2 S (and N and M) protein | 1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine breakthrough | Incidence of COVID-19 in participants throughout study period as self-reported or as determined by Luciferase Immunoprecipitation Systems assay/ELISA | Throughout the study period, until 36 months post-dose 3/4 | 
| Adverse events | Percentage of occurrence, types, duration and severity of adverse events and severe adverse events throughout study period | Throughout the study period, until 36 months post-dose 3/4 | 
| Binding anti-N antibody response | Geometric mean levels and geometric mean fold rise of SARS-CoV2 N-specific binding antibody as determined by Enzyme-linked Immunosorbent Assay in Arm C participants receiving CoronaVac | 1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4) |