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Safety and Immunogenicity of the ChadOx1 nCoV-19 (AZD1222) Vaccine in Children Aged 12-17 Years: A Preliminary Report of a Phase 2, Single-Blind, Randomised Controlled Trial (COV006)
43 Pages Posted: 20 Dec 2021
More...Abstract
Background: Vaccination of children and young people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended in some countries. There are few data on immune responses induced by COVID-19 vaccines in young people under the age of 18 years.MethodsCOV006 is a phase 1/2, single blind, randomised controlled trial in children and adolescents of ChadOx1 nCOV-19, at four trial sites in the UK. Healthy participants aged 6-17 years old were assigned to four arms (4:1:4:1), receiving either two doses of ChAdOx1 nCoV-19 or control (capsular group B meningococcal vaccine), 28 days (short interval) or 84 days (long-interval) apart. The primary outcome was to assess the safety and tolerability, with immunogenicity as a secondary outcome. This report includes findings from the 12-17 year-old participants.
Findings: Between 15th February 2021 and 2>nd April 2021, 150 eligible participants were randomly assigned to receive vaccination with 2 doses of either or ChAdOx1 nCoV-19 (n=120, 59 with short interval and 61 with long interval) or control (n=30). No SAEs related to ChAdOx1 nCoV-19 administration were recorded as of the data cut-off date. Solicited adverse reactions were reported more frequently after the first dose of ChAdOx1 nCoV-19 compared with the second dose. Increasing the interval between doses has a limited impact on the reactogenenicity of the second dose.
There were 10 (7%) baseline seropositive participants among 137 participants with available serostatus data. Among the seronegative participants who received ChAdOx1 nCoV-19, tanti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 post second dose were higher in those with a longer interval between doses (geometric means of 73371 AU/ml (95% CI 58685, 91733) and 287 IC50 (95% CI 218, 378)) compared with those who received their vaccines 28 days apart (43280 AU/ml (95% CI 35852, 52246) and 150 IC50 (95% CI 116, 194)). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 (geometric means of 302 (95% CI 233, 391) and 243 (95% CI 188, 314) SFC/106 PBMCs, in the short and long interval arms respectively), and remained above baseline after a second vaccination.
Interpretation: ChAdOx1 nCoV-19 (AZD1222) is well-tolerated and immunogenic in adolescents aged 12-17 years, inducing levels of antibody comparable to those associated with high efficacy in phase 3 efficacy studies in adults. No safety concerns were raised in this trial.
Trial Registration: An independent DSMB provided safety oversight for this trial, which is registered with ISRCTN number 15638344. A protocol is available on the ISRCTN website.
Funding: The study is funded by the Department of Health and Social Care, through the National Institute for
Health Research, and AstraZeneca.
Declaration of Interest: AJP is chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP is an NIHR Senior Investigator. AJP is chief investigator on clinical trials of Oxford University’s COVID19 vaccine funded by NIHR. TL is named as an inventor on a patent application covering the ChAd vaccine and is an occasional consultant to Vaccitech, unrelated to this work. Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Janssen, Medimmune, and MCM. He receives no personal financial payment for this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an investigator or provides consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers, including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck, and Valneva. He receives no personal financial payment for this work. PTH acts on behalf of St George’s University of London as an investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers, including Janssen, Pfizer, AstraZeneca, Novavax, and Valneva. He receives no personal financial payment for this work. All other authors declare no competing interests. AstraZeneca reviewed the final manuscript before submission, but the authors retained editorial control.
Ethical Approval: This study was approved by the Medicines and Healthcare products regulatory agency (MHRA) and the South Central Berkshire Research Ethics Committee.
Keywords: ChAdOx1 nCoV-19, AZD1222, Safety, Immunogenicity, Adolescent, COVID-19
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