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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BNT162b2 (adult/adolescent) | Experimental | 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 (intramuscular) | Experimental | 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 (intradermal) | Experimental | 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 (paediatric) | Experimental | BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (for immunocompromised patients only) 10ug/0.1ml per dose 4 doses for immunocompromised patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tozinameran | Biological | mRNA vaccine developed by BioNTech against COVID-19 |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
1. reported pregnancy or breastfeeding
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| Name | Affiliation | Role |
|---|---|---|
| Yu Lung Lau, MD | The University of Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Queen Mary Hospital | Hong Kong | Hong Kong | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35764637 | Derived | 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. |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000090982 | BNT162 Vaccine |
| C000722216 | sinovac COVID-19 vaccine |
| D007271 | Injections, Intradermal |
| ID | Term |
|---|---|
| D000087503 | mRNA Vaccines |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D011994 | Recombinant Proteins |
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| CoronaVac | Biological | Inactivated virus vaccine developed by SinoVac against COVID-19, intramuscular |
|
| CoronaVac, intradermal | Biological | Inactivated virus vaccine developed by SinoVac against COVID-19, intradermal |
|
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) |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D007279 | Injections, Subcutaneous |
| D007267 | Injections |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |