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Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial.
Stuart, Arabella S V; Shaw, Robert H; Liu, Xinxue; Greenland, Melanie; Aley, Parvinder K; Andrews, Nick J; Cameron, J C; Charlton, Sue; Clutterbuck, Elizabeth A; Collins, Andrea M; Darton, Tom; Dinesh, Tanya; Duncan, Christopher J A; England, Anna; Faust, Saul N; Ferreira, Daniela M; Finn, Adam; Goodman, Anna L; Green, Christopher A; Hallis, Bassam; Heath, Paul T; Hill, Helen; Horsington, Bryn M; Lambe, Teresa; Lazarus, Rajeka; Libri, Vincenzo; Lillie, Patrick J; Mujadidi, Yama F; Payne, Ruth; Plested, Emma L; Provstgaard-Morys, Samuel; Ramasamy, Maheshi N; Ramsay, Mary; Read, Robert C; Robinson, Hannah; Screaton, Gavin R; Singh, Nisha; Turner, David P J; Turner, Paul J; Vichos, Iason; White, Rachel; Nguyen-Van-Tam, Jonathan S; Snape, Matthew D.
Afiliación
  • Stuart ASV; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Shaw RH; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Liu X; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Greenland M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Aley PK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Andrews NJ; Statistics, Modelling and Economics Department, UK Health Security Agency, London, UK; Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK.
  • Cameron JC; Public Health Scotland, Glasgow, Scotland, UK.
  • Charlton S; UK Health Security Agency, Porton Down, Salisbury, UK.
  • Clutterbuck EA; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Collins AM; Liverpool School of Tropical Medicine, Liverpool, UK.
  • Darton T; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • Dinesh T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Duncan CJA; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle, UK.
  • England A; UK Health Security Agency, Porton Down, Salisbury, 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.
  • Ferreira DM; Liverpool School of Tropical Medicine, Liverpool, UK.
  • Finn A; School of Population Health Sciences, and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Goodman AL; Department of Infection, and NIHR BRC, Guy's and St Thomas' NHS Foundation Trust, London, UK; MRC Clinical Trials Unit, University College London, London, UK.
  • Green CA; NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
  • Hallis B; UK Health Security Agency, Porton Down, Salisbury, UK.
  • Heath PT; The Vaccine Institute, St George's University of London, London, UK.
  • Hill H; Liverpool School of Tropical Medicine, Liverpool, UK.
  • Horsington BM; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Lambe T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical, Science Oxford Institute, University of Oxford, Oxford, UK.
  • Lazarus R; North Bristol NHS Trust, Bristol, UK.
  • Libri V; NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
  • Lillie PJ; Infection Research Group, Hull University Teaching Hospitals NHS Trust, Hull, UK.
  • Mujadidi YF; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Payne R; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • Plested EL; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Provstgaard-Morys S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Ramasamy MN; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Ramsay M; Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, 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.
  • Robinson H; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Screaton GR; Chinese Academy of Medical, Science Oxford Institute, University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Singh N; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Turner DPJ; University of Nottingham, Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK.
  • Turner PJ; National Heart and Lung Institute, Imperial College London, London, UK.
  • Vichos I; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • White R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Nguyen-Van-Tam JS; Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.
  • Snape MD; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford NIHR-Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: matthew.snape@paediatrics.ox.ac.uk.
Lancet ; 399(10319): 36-49, 2022 01 01.
Article en En | MEDLINE | ID: mdl-34883053
BACKGROUND: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). METHODS: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. FINDINGS: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. INTERPRETATION: Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. FUNDING: UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Inmunización Secundaria / Inmunogenicidad Vacunal / Vacunas contra la COVID-19 / Vacunas de ARNm / Adyuvantes de Vacunas Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Lancet Año: 2022 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Inmunización Secundaria / Inmunogenicidad Vacunal / Vacunas contra la COVID-19 / Vacunas de ARNm / Adyuvantes de Vacunas Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Lancet Año: 2022 Tipo del documento: Article