Your browser doesn't support javascript.
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.
Liu, Xinxue; Shaw, Robert H; Stuart, Arabella S V; Greenland, Melanie; Aley, Parvinder K; Andrews, Nick J; Cameron, J Claire; Charlton, Sue; Clutterbuck, Elizabeth A; Collins, Andrea M; Dinesh, Tanya; England, Anna; Faust, Saul N; Ferreira, Daniela M; Finn, Adam; Green, Christopher A; Hallis, Bassam; Heath, Paul T; Hill, Helen; Lambe, Teresa; Lazarus, Rajeka; Libri, Vincenzo; Long, Fei; Mujadidi, Yama F; Plested, Emma L; Provstgaard-Morys, Samuel; Ramasamy, Maheshi N; Ramsay, Mary; Read, Robert C; Robinson, Hannah; Singh, Nisha; Turner, David P J; Turner, Paul J; Walker, Laura L; White, Rachel; Nguyen-Van-Tam, Jonathan S; Snape, Matthew D.
  • Liu X; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Shaw RH; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Stuart ASV; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Greenland M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Aley PK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Andrews NJ; Statistics, Modelling and Economics Department, Public Health England, London, UK; Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK.
  • Cameron JC; Health Protection Scotland, Glasgow, UK.
  • Charlton S; Public Health England, 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.
  • Dinesh T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • England A; Public Health England, Porton Down, Salisbury, 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; School of Population Health Sciences and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Green CA; NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Hallis B; Public Health England, 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; Jenner Institute, University of Oxford, Oxford, UK.
  • Lazarus R; North Bristol NHS Trust, Bristol, UK.
  • Libri V; NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
  • Long F; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Mujadidi YF; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, 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 Countermeasures Division, National Infection Service, Public Health England, 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.
  • 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 and Lung Institute, Imperial College London, London, UK.
  • Walker LL; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • White R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Nguyen-Van-Tam JS; Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.
  • Snape MD; 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.
Lancet ; 398(10303): 856-869, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1397746
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 (11111111) 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 (1111) 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Lancet Year: 2021 Document Type: Article Affiliation country: S0140-6736(21)01694-9

Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 Type of study: Controlled clinical trial / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Lancet Year: 2021 Document Type: Article Affiliation country: S0140-6736(21)01694-9