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Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial.
Kelly, Eimear; Greenland, Melanie; de Whalley, Philip C S; Aley, Parvinder K; Plested, Emma L; Singh, Nisha; Koleva, Stanislava; Tonner, Sharon; Macaulay, Grace C; Read, Robert C; Ramsay, Mary; Cameron, J Claire; Turner, David P J; Heath, Paul T; Bernatoniene, Jolanta; Connor, Philip; Cathie, Katrina; Faust, Saul N; Banerjee, Indraneel; Cantrell, Liberty; Mujadidi, Yama F; Belhadef, Hanane Trari; Clutterbuck, Elizabeth A; Anslow, Rachel; Valliji, Zara; James, Tim; Hallis, Bassam; Otter, Ashley David; Lambe, Teresa; Nguyen-Van-Tam, Jonathan S; Minassian, Angela M; Liu, Xinxue; Snape, Matthew D.
Afiliação
  • Kelly E; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Greenland M; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • de Whalley PCS; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Aley PK; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Plested EL; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Singh N; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Koleva S; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Tonner S; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Macaulay GC; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Read RC; NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Ramsay M; Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK.
  • Cameron JC; Health Protection Scotland, Glasgow, UK.
  • Turner DPJ; University of Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK.
  • Heath PT; Vaccine Institute, St. George's, University of London and St. George's University Hospitals NHS Trust, London, UK.
  • Bernatoniene J; Paediatric Infectious Disease and Immunology Department, Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, University of Bristol, UK.
  • Connor P; Noah's Ark Children's Hospital for Wales, University Hospital of Wales, Cardiff, UK.
  • Cathie K; NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Faust SN; NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Banerjee I; Royal Manchester Children's Hospital, Manchester University Hospitals Foundation Trust, UK.
  • Cantrell L; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Mujadidi YF; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Belhadef HT; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Clutterbuck EA; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Anslow R; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Valliji Z; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • James T; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Hallis B; UK Health Security Agency, Porton Down, Salisbury, UK.
  • Otter AD; UK Health Security Agency, Porton Down, Salisbury, UK.
  • Lambe T; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.
  • Nguyen-Van-Tam JS; Population and Lifespan Health, University of Nottingham, Nottingham, UK.
  • Minassian AM; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Biochemistry, University of Oxford, UK. Electronic address: angela.minassian@bioch.ox.ac.uk.
  • Liu X; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Snape MD; Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, Department of Paediatrics, University of Oxford, Oxford, UK.
J Infect ; 87(3): 230-241, 2023 09.
Article em En | MEDLINE | ID: mdl-37331429
ABSTRACT

BACKGROUND:

This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents.

METHODS:

A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (111) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory.

FINDINGS:

148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI) 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI 0.65, 1.54] and 1.02 [95% CI 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI 1.07, 2.69] and 1.43 [95% CI 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules.

INTERPRETATION:

Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule.

FUNDING:

National Institute for Health Research and Vaccine Task Force. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number registry 12348322.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra COVID-19 / COVID-19 Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra COVID-19 / COVID-19 Idioma: En Ano de publicação: 2023 Tipo de documento: Article