View in EDS

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.

Saved in:
Bibliographic Details
Title: 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.
Authors: Liu, Xinxue (AUTHOR), Shaw, Robert H (AUTHOR), Stuart, Arabella S V (AUTHOR), Greenland, Melanie (AUTHOR), Aley, Parvinder K (AUTHOR), Andrews, Nick J (AUTHOR), Cameron, J Claire (AUTHOR), Charlton, Sue (AUTHOR), Clutterbuck, Elizabeth A (AUTHOR), Collins, Andrea M (AUTHOR), Dinesh, Tanya (AUTHOR), England, Anna (AUTHOR), Faust, Saul N (AUTHOR), Ferreira, Daniela M (AUTHOR), Finn, Adam (AUTHOR), Green, Christopher A (AUTHOR), Hallis, Bassam (AUTHOR), Heath, Paul T (AUTHOR), Hill, Helen (AUTHOR), Lambe, Teresa (AUTHOR)
Source: Lancet. Sep2021, Vol. 398 Issue 10303, p856-869. 14p.
Subjects: COVID-19 vaccines, COVID-19, Vaccine safety, SARS-CoV-2, Immunoglobulin G
Geographic Terms: Chad
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. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 152204747
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: 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.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Liu%2C+Xinxue%22">Liu, Xinxue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shaw%2C+Robert+H%22">Shaw, Robert H</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stuart%2C+Arabella+S+V%22">Stuart, Arabella S V</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Greenland%2C+Melanie%22">Greenland, Melanie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Aley%2C+Parvinder+K%22">Aley, Parvinder K</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Andrews%2C+Nick+J%22">Andrews, Nick J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cameron%2C+J+Claire%22">Cameron, J Claire</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Charlton%2C+Sue%22">Charlton, Sue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Clutterbuck%2C+Elizabeth+A%22">Clutterbuck, Elizabeth A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Collins%2C+Andrea+M%22">Collins, Andrea M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dinesh%2C+Tanya%22">Dinesh, Tanya</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22England%2C+Anna%22">England, Anna</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Faust%2C+Saul+N%22">Faust, Saul N</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ferreira%2C+Daniela+M%22">Ferreira, Daniela M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Finn%2C+Adam%22">Finn, Adam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Green%2C+Christopher+A%22">Green, Christopher A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hallis%2C+Bassam%22">Hallis, Bassam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Heath%2C+Paul+T%22">Heath, Paul T</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hill%2C+Helen%22">Hill, Helen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lambe%2C+Teresa%22">Lambe, Teresa</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. Sep2021, Vol. 398 Issue 10303, p856-869. 14p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22COVID-19+vaccines%22">COVID-19 vaccines</searchLink><br /><searchLink fieldCode="DE" term="%22COVID-19%22">COVID-19</searchLink><br /><searchLink fieldCode="DE" term="%22Vaccine+safety%22">Vaccine safety</searchLink><br /><searchLink fieldCode="DE" term="%22SARS-CoV-2%22">SARS-CoV-2</searchLink><br /><searchLink fieldCode="DE" term="%22Immunoglobulin+G%22">Immunoglobulin G</searchLink>
– Name: SubjectGeographic
  Label: Geographic Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Chad%22">Chad</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Findings: </bold>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.<bold>Interpretation: </bold>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.<bold>Funding: </bold>UK Vaccine Task Force and National Institute for Health Research. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=152204747
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/S0140-6736(21)01694-9
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 14
        StartPage: 856
    Subjects:
      – SubjectFull: COVID-19 vaccines
        Type: general
      – SubjectFull: COVID-19
        Type: general
      – SubjectFull: Vaccine safety
        Type: general
      – SubjectFull: SARS-CoV-2
        Type: general
      – SubjectFull: Immunoglobulin G
        Type: general
      – SubjectFull: Chad
        Type: general
    Titles:
      – TitleFull: 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.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Liu, Xinxue
      – PersonEntity:
          Name:
            NameFull: Shaw, Robert H
      – PersonEntity:
          Name:
            NameFull: Stuart, Arabella S V
      – PersonEntity:
          Name:
            NameFull: Greenland, Melanie
      – PersonEntity:
          Name:
            NameFull: Aley, Parvinder K
      – PersonEntity:
          Name:
            NameFull: Andrews, Nick J
      – PersonEntity:
          Name:
            NameFull: Cameron, J Claire
      – PersonEntity:
          Name:
            NameFull: Charlton, Sue
      – PersonEntity:
          Name:
            NameFull: Clutterbuck, Elizabeth A
      – PersonEntity:
          Name:
            NameFull: Collins, Andrea M
      – PersonEntity:
          Name:
            NameFull: Dinesh, Tanya
      – PersonEntity:
          Name:
            NameFull: England, Anna
      – PersonEntity:
          Name:
            NameFull: Faust, Saul N
      – PersonEntity:
          Name:
            NameFull: Ferreira, Daniela M
      – PersonEntity:
          Name:
            NameFull: Finn, Adam
      – PersonEntity:
          Name:
            NameFull: Green, Christopher A
      – PersonEntity:
          Name:
            NameFull: Hallis, Bassam
      – PersonEntity:
          Name:
            NameFull: Heath, Paul T
      – PersonEntity:
          Name:
            NameFull: Hill, Helen
      – PersonEntity:
          Name:
            NameFull: Lambe, Teresa
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 04
              M: 09
              Text: Sep2021
              Type: published
              Y: 2021
          Identifiers:
            – Type: issn-print
              Value: 01406736
          Numbering:
            – Type: volume
              Value: 398
            – Type: issue
              Value: 10303
          Titles:
            – TitleFull: Lancet
              Type: main
ResultId 1