Evidence map›Paper›PMID 34863358›Full record

Trial reportLancet (London, England)2021

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.

Alasdair P S Munro, Leila Janani, Victoria Cornelius, Parvinder K Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Kate Dodd and 45 more

Erratum issued 2 registry-linked trialsAbstract readClinical Trial, Phase IIComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 431 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
431citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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.

NCT05228730 phase3terminatednot on this mapstarted 2022, after this paper: background citation

A Randomised Controlled Trial to Assess the Immunogenicity, Safety, and Reactogenicity of Standard-dose Versus Fractional Doses of COVID-19 Vaccines (Pfizer-BioNTech or Moderna) Given as an Additional Dose After Priming With Pfizer-BioNTech or AstraZeneca in Healthy Adults in Australia-MIACoV

TypeinterventionalSponsorMurdoch Childrens Research InstituteRan2022 to 2022Enrolled13ConditionsCOVID-19ArmsTozinameran - Standard dose, Tozinameran - fractional dose, Elasomeran - standard dose, Elasomeran - fractional dose
NCT05265065 phase3completednot on this mapstarted 2022, after this paper: background citation

A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity of Standard Dose Versus Fractional Doses of COVID-19 Vaccine (Pfizer-BioNTech) Given as a Booster Dose After Priming With Sinopharm, AstraZeneca or Sputnik in Healthy Adults in Mongolia

TypeinterventionalSponsorMurdoch Childrens Research InstituteRan2022 to 2024Enrolled601ConditionsCOVID-19ArmsTozinameran - Standard Dose, Tozinameran - Fractional Dose
3 · Its place in the literature

Who cites it

431 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  18. Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
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371 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors.

Alasdair P S MunroNIHR 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.
Leila JananiImperial Clinical Trials Unit, Imperial College London, London, UK.
Victoria CorneliusImperial Clinical Trials Unit, Imperial College London, London, UK.
Parvinder K AleyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Gavin BabbageNIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
David BaxterStockport NHS Foundation Trust, Stockport, UK.
Marcin BulaNIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.
Katrina CathieNIHR 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.
Krishna ChatterjeeNIHR Cambridge Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Kate DoddNIHR Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.
Yvanne EneverPHARMExcel, Welwyn Garden City, Hertfordshire, UK.
Karishma GokaniNIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Anna L GoodmanDepartment of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK; MRC Clinical Trials Unit, University College London, London, UK.
Christopher A GreenNIHR/Wellcome Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Linda HarndahlPortsmouth Hospitals University NHS Trust, Portsmouth, UK.
John HaughneyQueen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK.
Alexander HicksPortsmouth Hospitals University NHS Trust, Portsmouth, UK.
Agatha A van der KlaauwWellcome-MRC Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
Jonathan KwokCancer Research UK Oxford Centre, University of Oxford, Oxford, UK.
Teresa LambeOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Vincenzo LibriNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
Martin J LlewelynUniversity Hospitals Sussex NHS Foundation Trust, Brighton, UK.
Alastair C McGregorDepartment of Infectious Diseases and Tropical Medicine, London Northwest University Healthcare, London, UK.
Angela M MinassianOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Patrick MooreThe Adam Practice, Poole, UK.
Mehmood MughalStockport NHS Foundation Trust, Stockport, UK.
Yama F MujadidiOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Jennifer MuriraNIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK.
Orod OsanlouNorth Wales Clinical Research Facility, Betsi Cadwaladr University Health Board and Bangor University, Bangor, UK.
Rostam OsanlouDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Daniel R OwensNIHR 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.
Mihaela PacurarNIHR 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.
Adrian PalfreemanUniversity Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK.
Daniel PanUniversity Hospitals of Leicester NHS Trust, University of Leicester, Leicester, UK.
Tommy RamplingNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
Karen ReganBradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Stephen SaichNIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Jo SalkeldDepartment of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Dinesh SaralayaBradford Institute for Health Research and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Sunil SharmaUniversity Hospitals Sussex NHS Foundation Trust, Brighton, UK.
Ray SheridanRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.
Ann SturdyDepartment of Infectious Diseases and Tropical Medicine, London Northwest University Healthcare, London, UK.
Emma C ThomsonQueen Elizabeth University Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK; MRC University of Glasgow Centre for Virus Research, Glasgow, UK.
Shirley ToddRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.
Chris TwelvesNIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, 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.
Sue CharltonUK Health Security Agency, Porton Down, UK.
Bassam HallisUK Health Security Agency, Porton Down, UK.
Mary RamsayUK Health Security Agency, Colindale, London, UK.
Nick AndrewsUK Health Security Agency, Colindale, London, UK.
Jonathan S Nguyen-Van-TamDivision of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.
Matthew D SnapeOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
Xinxue LiuOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, 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. Electronic address: s.faust@soton.ac.uk.
COV-BOOST study group

Funding

Medical Research Council MC_PC_19026Medical Research Council MC_UU_00004/04Medical Research Council MR/K002597/1Medical Research Council MR/N013204/1Medical Research Council MR/N026993/1
6 · The paper itself

Abstract

backgroundFew data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT).

methodsCOV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.

findingsBetween June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.

interpretationAll study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.

fundingUK Vaccine Taskforce and National Institute for Health Research.

Indexed as

Immunogenicity, VaccineAdultAgedAged, 80 and overBNT162 VaccineChAdOx1 nCoV-19COVID-19FemaleHumansImmunization, SecondaryMaleMiddle AgedPandemicsPatient SafetySARS-CoV-2United KingdomBNT162 VaccineChAdOx1 nCoV-19

Identifiers

PMID34863358
PMCPMC8639161

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Registered trials

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.