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.

Autor:	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.
Jazyk:	angličtina
Zdroj:	The Journal of infection [J Infect] 2023 Jun; Vol. 86 (6), pp. 574-583. Date of Electronic Publication: 2023 Apr 06.
DOI:	10.1016/j.jinf.2023.03.027
Abstrakt:	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 1:1:1 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% CI:2.5,3.5) to 2.4 (95% CI:1.9, 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 EudraCT:2021-001275-16. Competing Interests: Declaration of interests At the time of this study, MDS acted 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 vaccines. He received no personal financial payment for this work. Subsequent to this study MDS is employed by Moderna Biotech UK and holds equity in this company. Moderna Biotech had no role in the study design, analysis of data or interpretation of results. JSN-V-T was seconded to the Department of Health and Social Care (DHSC), England from October 2017 to March 2022; since leaving DHSC he reports a lecture fee from AstraZeneca. AMC and DMF are investigators on studies funded by Pfizer and Unilever. They receive no personal financial payment for this work. AF is a member of the Joint Committee on Vaccination and Immunisation and chair of the WHO European Technical Advisory Group of Experts (ETAGE) on Immunisation. He is an investigator and/or provides consultative advice on clinical trials and studies of COVID-19 vaccines produced by AstraZeneca, Janssen, Valneva, Pfizer, and Sanofi, and of other vaccines from these and other manufacturers, including GlaxoSmithKline, VPI Pharmaceuticals, Takeda, and Bionet Asia. He receives no personal remuneration or benefits for any of this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an investigator and/or providing 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 vaccines and antimicrobials. 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. CAG acts on behalf of University Hospitals Birmingham NHS Foundation Trust as an investigator on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers, including Janssen, Pfizer, AstraZeneca, Novavax, CureVac, Moderna, and Valneva. He receives no personal financial payment for this work. VL acts on behalf of University College London Hospitals NHS Foundation Trust as an investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Pfizer, AstraZeneca, and Valneva. He receives no personal financial payment for this work. 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. ALG is named as an inventor on a patent covering use of a particular promoter construct that is often used in -vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine. ALG may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the University’s revenue sharing policy. Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. All other authors declare no competing interests. The views expressed in this manuscript are those of its authors and not necessarily those of DHSC, VTF or NIHR. (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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