Evidence map›Paper›PMID 37028454›Full record

Trial reportThe Journal of infection2023

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.

Robert H Shaw, Melanie Greenland, Arabella S V Stuart, Parvinder K Aley, Nick J Andrews, J Claire Cameron, Sue Charlton, Elizabeth A Clutterbuck, Andrea M Collins, Tom Darton and 31 more

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of infection, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Observational
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

41 authors at 16 institutions in 1 country.

Robert H ShawOxford 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.
Melanie GreenlandOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Arabella S V StuartOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Parvinder K AleyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Nick J AndrewsImmunisation and Vaccine Preventable Diseases Division, UK Health Security Agency, London, UK.
J Claire CameronPublic Health Scotland, Glasgow, Scotland, UK.
Sue CharltonUK Health Security Agency, Porton Down, Salisbury, UK.
Elizabeth A ClutterbuckOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Andrea M CollinsLiverpool School of Tropical Medicine, Liverpool, UK.
Tom DartonDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, UK.
Tanya DineshOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Christopher J A DuncanThe Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; Translational and Clinical Research Institute, Newcastle University, UK.
Saul N FaustNIHR 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.
Daniela M FerreiraLiverpool School of Tropical Medicine, Liverpool, UK.
Adam FinnSchools of Population Health Sciences and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Anna L GoodmanDepartment of Infection & NIHR BRC, Guy's and St Thomas' NHS Foundation Trust, UK; MRC Clinical Trials Unit, University College London, UK.
Christopher A GreenNIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; School of Chemical Engineering, University of Birmingham, UK.
Bassam HallisUK Health Security Agency, Porton Down, Salisbury, UK.
Paul T HeathThe Vaccine Institute, St. George's University of London, London, UK.
Helen HillLiverpool School of Tropical Medicine, Liverpool, UK.
Teresa LambeOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Vincenzo LibriNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
Patrick J LillieInfection Research Group, Hull University Teaching Hospitals NHS Trust, Hull, UK.
Ella MoreyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Yama F MujadidiOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Ruth PayneDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, UK.
Emma L PlestedOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Samuel Provstgaard-MorysOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Maheshi N RamasamyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Mary RamsayImmunisation and Vaccine Preventable Diseases Division, UK Health Security Agency, London, UK.
Robert C ReadNIHR 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.
Hannah RobinsonOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Gavin R ScreatonChinese 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.
Nisha SinghOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
David P J TurnerUniversity of Nottingham, Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK.
Paul J TurnerNational Heart & Lung Institute, Imperial College London, London, UK.
Rachel WhiteOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Jonathan S Nguyen-Van-TamUnit of Lifespan and Population Health, University of Nottingham School of Medicine, Nottingham, UK.
Xinxue LiuOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Matthew D SnapeOxford NIHR - Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Com-COV2 Study Group
University of Oxford · GBUK Health Security Agency · GBLiverpool School of Tropical Medicine · GBSheffield Teaching Hospitals NHS Foundation Trust · GBUniversity Hospital Southampton NHS Foundation Trust · GBCentre for Human Genetics · GBGuy's and St Thomas' NHS Foundation Trust · GBImperial College London · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBNottingham University Hospitals NHS Trust · GBPublic Health Scotland · GBSt George's, University of London · GBUCL Biomedical Research Centre · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity of Bristol · GBUniversity of Nottingham · GB

Funding

Department of Health NIHR202851Department of Health PR-R17-0916-22001Medical Research Council MC_UU_00004/04Medical Research Council MR/X001598/1
6 · The paper itself

Abstract

backgroundHeterologous 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.

methodsCom-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.

findingsIn 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.

interpretationHeterologous 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.

Indexed as

COVID-19VaccinesAdultAntibodies, ViralBNT162 VaccineChAdOx1 nCoV-19COVID-19 VaccinesFemaleHumansImmunityImmunoglobulin GMalePandemicsSingle-Blind MethodVaccinationAntibodies, ViralBNT162 VaccineChAdOx1 nCoV-19COVID-19 VaccinesImmunoglobulin GVaccinesAdenovirus vectorAntibodyHeterologousmRNA lipid nanoparticlePersistenceSARS-CoV2T-cellVaccine

Identifiers

PMID37028454
PMCPMC10076082
OpenAlexW4362636646

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.