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Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - A single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines.
Shaw, Robert H; Greenland, Melanie; Stuart, Arabella S V; Aley, Parvinder K; Andrews, Nick J; Cameron, J Claire; Charlton, Sue; Clutterbuck, Elizabeth A; Collins, Andrea M; Darton, Tom; Dinesh, Tanya; Duncan, Christopher J A; Faust, Saul N; Ferreira, Daniela M; Finn, Adam; Goodman, Anna L; Green, Christopher A; Hallis, Bassam; Heath, Paul T; Hill, Helen; Lambe, Teresa; Libri, Vincenzo; Lillie, Patrick J; Morey, Ella; 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; White, Rachel; Nguyen-Van-Tam, Jonathan S; Liu, Xinxue; Snape, Matthew D.
  • Shaw RH; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: robert.shaw@paediatrics.ox.ac.uk.
  • Greenland M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Stuart ASV; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Aley PK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Andrews NJ; Immunisation and Vaccine Preventable Diseases Division, 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, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, UK.
  • Dinesh T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Duncan CJA; The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; Translational and Clinical Research Institute, Newcastle University, 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; Schools of Population Health Sciences and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Goodman AL; Department of Infection & NIHR BRC, Guy's and St Thomas' NHS Foundation Trust, UK; MRC Clinical Trials Unit, University College London, UK.
  • Green CA; NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; School of Chemical Engineering, University of 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.
  • Lambe T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, 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.
  • Morey E; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, 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, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, 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 Vaccine Preventable Diseases Division, 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 (CAMS) Oxford Institute (COI), 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 & Lung Institute, Imperial College London, London, UK.
  • White R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Nguyen-Van-Tam JS; Unit of Lifespan and Population Health, University of Nottingham School of Medicine, Nottingham, UK.
  • Liu X; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Snape MD; Oxford NIHR - Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
J Infect ; 86(6): 574-583, 2023 06.
Article in English | MEDLINE | ID: covidwho-2303587
ABSTRACT

BACKGROUND:

Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development.

METHODS:

Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 111 to receive a second dose 8-12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration.

FINDINGS:

In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval) 8.2, 11.5) at D28 to 6.2 (95% CI 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI2.5,3.5) to 2.4 (95% CI1.9, 3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI 1.17, 1.58) at D28 to 1.52 (95% CI 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI 0.47, 0.64) at day 28 and 0.62 (95% CI 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies.

INTERPRETATION:

Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN 27841311 EudraCT2021-001275-16.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / COVID-19 Type of study: Cohort study / Experimental Studies / Prognostic study / Qualitative research / Randomized controlled trials Topics: Vaccines Limits: Adult / Female / Humans / Male Language: English Journal: J Infect Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / COVID-19 Type of study: Cohort study / Experimental Studies / Prognostic study / Qualitative research / Randomized controlled trials Topics: Vaccines Limits: Adult / Female / Humans / Male Language: English Journal: J Infect Year: 2023 Document Type: Article