Tags

Type your tag names separated by a space and hit enter

Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial.
Lancet. 2021 09 04; 398(10303):856-869.Lct

Abstract

BACKGROUND

Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer-BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines.

METHODS

Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139.

FINDINGS

Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation.

INTERPRETATION

Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.

FUNDING

UK Vaccine Task Force and National Institute for Health Research.

Authors+Show Affiliations

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Statistics, Modelling and Economics Department, Public Health England, London, UK; Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK.Health Protection Scotland, Glasgow, UK.Public Health England, Porton Down, Salisbury, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Liverpool School of Tropical Medicine, Liverpool, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Public Health England, Porton Down, Salisbury, UK.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.Liverpool School of Tropical Medicine, Liverpool, UK.School of Population Health Sciences and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.Public Health England, Porton Down, Salisbury, UK.The Vaccine Institute, St George's University of London, London, UK.Liverpool School of Tropical Medicine, Liverpool, UK.Jenner Institute, University of Oxford, Oxford, UK.North Bristol NHS Trust, Bristol, UK.NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK.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.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.University of Nottingham, Nottingham, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK.National Heart and Lung Institute, Imperial College London, London, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: matthew.snape@paediatrics.ox.ac.uk.No affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34370971

Citation

Liu, Xinxue, et al. "Safety and Immunogenicity of Heterologous Versus Homologous Prime-boost Schedules With an Adenoviral Vectored and mRNA COVID-19 Vaccine (Com-COV): a Single-blind, Randomised, Non-inferiority Trial." Lancet (London, England), vol. 398, no. 10303, 2021, pp. 856-869.
Liu X, Shaw RH, Stuart ASV, et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet. 2021;398(10303):856-869.
Liu, X., Shaw, R. H., Stuart, A. S. V., Greenland, M., Aley, P. K., Andrews, N. J., Cameron, J. C., Charlton, S., Clutterbuck, E. A., Collins, A. M., Dinesh, T., England, A., Faust, S. N., Ferreira, D. M., Finn, A., Green, C. A., Hallis, B., Heath, P. T., Hill, H., ... Snape, M. D. (2021). Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet (London, England), 398(10303), 856-869. https://doi.org/10.1016/S0140-6736(21)01694-9
Liu X, et al. Safety and Immunogenicity of Heterologous Versus Homologous Prime-boost Schedules With an Adenoviral Vectored and mRNA COVID-19 Vaccine (Com-COV): a Single-blind, Randomised, Non-inferiority Trial. Lancet. 2021 09 4;398(10303):856-869. PubMed PMID: 34370971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. AU - Liu,Xinxue, AU - Shaw,Robert H, AU - Stuart,Arabella S V, AU - Greenland,Melanie, AU - Aley,Parvinder K, AU - Andrews,Nick J, AU - Cameron,J Claire, AU - Charlton,Sue, AU - Clutterbuck,Elizabeth A, AU - Collins,Andrea M, AU - Dinesh,Tanya, AU - England,Anna, AU - Faust,Saul N, AU - Ferreira,Daniela M, AU - Finn,Adam, AU - Green,Christopher A, AU - Hallis,Bassam, AU - Heath,Paul T, AU - Hill,Helen, AU - Lambe,Teresa, AU - Lazarus,Rajeka, AU - Libri,Vincenzo, AU - Long,Fei, AU - Mujadidi,Yama F, AU - Plested,Emma L, AU - Provstgaard-Morys,Samuel, AU - Ramasamy,Maheshi N, AU - Ramsay,Mary, AU - Read,Robert C, AU - Robinson,Hannah, AU - Singh,Nisha, AU - Turner,David P J, AU - Turner,Paul J, AU - Walker,Laura L, AU - White,Rachel, AU - Nguyen-Van-Tam,Jonathan S, AU - Snape,Matthew D, AU - ,, Y1 - 2021/08/06/ PY - 2021/06/25/received PY - 2021/07/08/revised PY - 2021/07/20/accepted PY - 2021/8/10/pubmed PY - 2021/9/16/medline PY - 2021/8/9/entrez SP - 856 EP - 869 JF - Lancet (London, England) JO - Lancet VL - 398 IS - 10303 N2 - BACKGROUND: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer-BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. METHODS: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. FINDINGS: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. INTERPRETATION: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. FUNDING: UK Vaccine Task Force and National Institute for Health Research. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/34370971/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(21)01694-9 DB - PRIME DP - Unbound Medicine ER -