Covid-19 Vaccination in Adolescents and Children (COVAC)

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

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.

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

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

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

BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (for immunocompromised patients only) 10ug/0.1ml per dose 4 doses for immunocompromised patients

Geometric mean levels of SARS-CoV2 S and S-RBD-specific binding antibody and related markers as determined by Enzyme-linked Immunosorbent Assay

Geometric mean levels and geometric mean fold rise of SARS-CoV2 neutralizing antibodies as determined by plaque reduction neutralization assay and surrogate assays

Incidence of COVID-19 in participants throughout study period as self-reported or as determined by Luciferase Immunoprecipitation Systems assay/ELISA

Percentage of occurrence, types, duration and severity of adverse events and severe adverse events throughout study period

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

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

Rosa Duque JS, Wang X, Leung D, Cheng SMS, Cohen CA, Mu X, Hachim A, Zhang Y, Chan SM, Chaothai S, Kwan KKH, Chan KCK, Li JKC, Luk LLH, Tsang LCH, Wong WHS, Cheang CH, Hung TK, Lam JHY, Chua GT, Tso WWY, Ip P, Mori M, Kavian N, Leung WH, Valkenburg S, Peiris M, Tu W, Lau YL. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents. Nat Commun. 2022 Jun 28;13(1):3700. doi: 10.1038/s41467-022-31485-z. Erratum In: Nat Commun. 2022 Aug 15;13(1):4798.