Arabella S V Stuart1, Robert H Shaw1, Xinxue Liu2, Melanie Greenland2, Parvinder K Aley2, Nick J Andrews3, J C Cameron4, Sue Charlton5, Elizabeth A Clutterbuck2, Andrea M Collins6, Tom Darton7, Tanya Dinesh2, Christopher J A Duncan8, Anna England5, Saul N Faust9, Daniela M Ferreira6, Adam Finn10, Anna L Goodman11, Christopher A Green12, Bassam Hallis5, Paul T Heath13, Helen Hill6, Bryn M Horsington2, Teresa Lambe14, Rajeka Lazarus15, Vincenzo Libri16, Patrick J Lillie17, Yama F Mujadidi2, Ruth Payne7, Emma L Plested2, Samuel Provstgaard-Morys2, Maheshi N Ramasamy1, Mary Ramsay18, Robert C Read9, Hannah Robinson2, Gavin R Screaton19, Nisha Singh2, David P J Turner20, Paul J Turner21, Iason Vichos2, Rachel White2, Jonathan S Nguyen-Van-Tam22, Matthew D Snape23. 1. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 2. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. 3. Statistics, Modelling and Economics Department, UK Health Security Agency, London, UK; Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK. 4. Public Health Scotland, Glasgow, Scotland, UK. 5. UK Health Security Agency, Porton Down, Salisbury, UK. 6. Liverpool School of Tropical Medicine, Liverpool, UK. 7. 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. 8. The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle, UK. 9. 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. 10. School of Population Health Sciences, and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK. 11. 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. 12. NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. 13. The Vaccine Institute, St George's University of London, London, UK. 14. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical, Science Oxford Institute, University of Oxford, Oxford, UK. 15. North Bristol NHS Trust, Bristol, UK. 16. NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK. 17. Infection Research Group, Hull University Teaching Hospitals NHS Trust, Hull, UK. 18. Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK. 19. 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. 20. University of Nottingham, Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK. 21. National Heart and Lung Institute, Imperial College London, London, UK. 22. Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK. 23. 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.
Abstract
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.
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.
Authors: Donna Rose Addis; R Shayna Rosenbaum; Julia G Halilova; Samuel Fynes-Clinton; Leonard Green; Joel Myerson; Jianhong Wu; Kai Ruggeri Journal: Sci Rep Date: 2022-07-13 Impact factor: 4.996
Authors: Alasdair P S Munro; Leila Janani; Victoria Cornelius; Parvinder K Aley; Gavin Babbage; David Baxter; Marcin Bula; Katrina Cathie; Krishna Chatterjee; Kate Dodd; Yvanne Enever; Karishma Gokani; Anna L Goodman; Christopher A Green; Linda Harndahl; John Haughney; Alexander Hicks; Agatha A van der Klaauw; Jonathan Kwok; Teresa Lambe; Vincenzo Libri; Martin J Llewelyn; Alastair C McGregor; Angela M Minassian; Patrick Moore; Mehmood Mughal; Yama F Mujadidi; Jennifer Murira; Orod Osanlou; Rostam Osanlou; Daniel R Owens; Mihaela Pacurar; Adrian Palfreeman; Daniel Pan; Tommy Rampling; Karen Regan; Stephen Saich; Jo Salkeld; Dinesh Saralaya; Sunil Sharma; Ray Sheridan; Ann Sturdy; Emma C Thomson; Shirley Todd; Chris Twelves; Robert C Read; Sue Charlton; Bassam Hallis; Mary Ramsay; Nick Andrews; Jonathan S Nguyen-Van-Tam; Matthew D Snape; Xinxue Liu; Saul N Faust Journal: Lancet Date: 2021-12-02 Impact factor: 202.731