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

the Com-COV2 Study Group

doi:10.1016/j.jinf.2023.03.027

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

the Com-COV2 Study Group

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Background: Heterologous 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. Methods: Com-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. Findings: In 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. Interpretation: Heterologous 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.

Original language	English
Pages (from-to)	574-583
Number of pages	10
Journal	Journal of Infection
Volume	86
Issue number	6
DOIs	https://doi.org/10.1016/j.jinf.2023.03.027
Publication status	Published - Jun 2023

Bibliographical note

Funding Information:
The study is funded by the UK Government through the National Institute for Health Research (NIHR) - grant ID NIHR202851, the Vaccine Task Force (VTF) and the Coalition for Epidemic Preparedness Innovations (CEPI). This research was supported by the NIHR Oxford Biomedical Research Centre, NIHR Guy's and St Thomas' Biomedical Research Centre, NIHR King's Clinical Research Facility and NIHR Policy Research Programme (PR-R17-0916-22001), the Southampton NIHR Biomedical Research Centre and Southampton NIHR Clinical Research Facility and delivered through the NIHR-funded National Immunisation Schedule Evaluation Consortium (NISEC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care (DHSC). NVX-CoV2373 vaccine was supplied for use in the trial by Novavax, Inc. MDS and SNF are NIHR senior investigators. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The investigators express their gratitude for the contribution of all trial participants, and for the invaluable advice of the data safety monitoring board. We additionally acknowledge the broader support from the various teams within the University of Oxford, including the Department of Paediatrics, Clinical Trials Research Governance, Research Contracts, and the Public Affairs Directorate.

Publisher Copyright:
© 2023 The Authors

Keywords

Adenovirus vector
Antibody
Heterologous
Persistence
SARS-CoV2
T-cell
Vaccine
mRNA lipid nanoparticle

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jinf.2023.03.027

Cite this

@article{59d8434d42104293b3d9b03f5c079e28,

title = "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",

abstract = "Background: Heterologous 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. Methods: Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose {\textquoteleft}ChAd{\textquoteright} (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or {\textquoteleft}BNT{\textquoteright} (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 {\textquoteleft}Mod{\textquoteright} (mRNA-1273, Spikevax, Moderna) or {\textquoteleft}NVX{\textquoteright} (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. Findings: In 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. Interpretation: Heterologous 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.",

keywords = "Adenovirus vector, Antibody, Heterologous, Persistence, SARS-CoV2, T-cell, Vaccine, mRNA lipid nanoparticle",

author = "{the Com-COV2 Study Group} and Shaw, {Robert H.} and Melanie Greenland and Stuart, {Arabella S.V.} and Aley, {Parvinder K.} and Andrews, {Nick J.} and Cameron, {J. Claire} and Sue Charlton and Clutterbuck, {Elizabeth A.} and Collins, {Andrea M.} and Tom Darton and Tanya Dinesh and Duncan, {Christopher J.A.} and Faust, {Saul N.} and Ferreira, {Daniela M.} and Adam Finn and Goodman, {Anna L.} and Green, {Christopher A.} and Bassam Hallis and Heath, {Paul T.} and Helen Hill and Teresa Lambe and Vincenzo Libri and Lillie, {Patrick J.} and Ella Morey and Mujadidi, {Yama F.} and Ruth Payne and Plested, {Emma L.} and Samuel Provstgaard-Morys and Ramasamy, {Maheshi N.} and Mary Ramsay and Read, {Robert C.} and Hannah Robinson and Screaton, {Gavin R.} and Nisha Singh and Turner, {David P.J.} and Turner, {Paul J.} and Rachel White and Nguyen-Van-Tam, {Jonathan S.} and Xinxue Liu and Snape, {Matthew D.}",

note = "Funding Information: The study is funded by the UK Government through the National Institute for Health Research (NIHR) - grant ID NIHR202851, the Vaccine Task Force (VTF) and the Coalition for Epidemic Preparedness Innovations (CEPI). This research was supported by the NIHR Oxford Biomedical Research Centre, NIHR Guy's and St Thomas' Biomedical Research Centre, NIHR King's Clinical Research Facility and NIHR Policy Research Programme (PR-R17-0916-22001), the Southampton NIHR Biomedical Research Centre and Southampton NIHR Clinical Research Facility and delivered through the NIHR-funded National Immunisation Schedule Evaluation Consortium (NISEC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care (DHSC). NVX-CoV2373 vaccine was supplied for use in the trial by Novavax, Inc. MDS and SNF are NIHR senior investigators. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The investigators express their gratitude for the contribution of all trial participants, and for the invaluable advice of the data safety monitoring board. We additionally acknowledge the broader support from the various teams within the University of Oxford, including the Department of Paediatrics, Clinical Trials Research Governance, Research Contracts, and the Public Affairs Directorate. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jun,

doi = "10.1016/j.jinf.2023.03.027",

language = "English",

volume = "86",

pages = "574--583",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "British Infection Society",

number = "6",

}

TY - JOUR

T1 - 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

AU - the Com-COV2 Study Group

AU - Shaw, Robert H.

AU - Greenland, Melanie

AU - Stuart, Arabella S.V.

AU - Aley, Parvinder K.

AU - Andrews, Nick J.

AU - Cameron, J. Claire

AU - Charlton, Sue

AU - Clutterbuck, Elizabeth A.

AU - Collins, Andrea M.

AU - Darton, Tom

AU - Dinesh, Tanya

AU - Duncan, Christopher J.A.

AU - Faust, Saul N.

AU - Ferreira, Daniela M.

AU - Finn, Adam

AU - Goodman, Anna L.

AU - Green, Christopher A.

AU - Hallis, Bassam

AU - Heath, Paul T.

AU - Hill, Helen

AU - Lambe, Teresa

AU - Libri, Vincenzo

AU - Lillie, Patrick J.

AU - Morey, Ella

AU - Mujadidi, Yama F.

AU - Payne, Ruth

AU - Plested, Emma L.

AU - Provstgaard-Morys, Samuel

AU - Ramasamy, Maheshi N.

AU - Ramsay, Mary

AU - Read, Robert C.

AU - Robinson, Hannah

AU - Screaton, Gavin R.

AU - Singh, Nisha

AU - Turner, David P.J.

AU - Turner, Paul J.

AU - White, Rachel

AU - Nguyen-Van-Tam, Jonathan S.

AU - Liu, Xinxue

AU - Snape, Matthew D.

N1 - Funding Information: The study is funded by the UK Government through the National Institute for Health Research (NIHR) - grant ID NIHR202851, the Vaccine Task Force (VTF) and the Coalition for Epidemic Preparedness Innovations (CEPI). This research was supported by the NIHR Oxford Biomedical Research Centre, NIHR Guy's and St Thomas' Biomedical Research Centre, NIHR King's Clinical Research Facility and NIHR Policy Research Programme (PR-R17-0916-22001), the Southampton NIHR Biomedical Research Centre and Southampton NIHR Clinical Research Facility and delivered through the NIHR-funded National Immunisation Schedule Evaluation Consortium (NISEC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care (DHSC). NVX-CoV2373 vaccine was supplied for use in the trial by Novavax, Inc. MDS and SNF are NIHR senior investigators. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The investigators express their gratitude for the contribution of all trial participants, and for the invaluable advice of the data safety monitoring board. We additionally acknowledge the broader support from the various teams within the University of Oxford, including the Department of Paediatrics, Clinical Trials Research Governance, Research Contracts, and the Public Affairs Directorate. Publisher Copyright: © 2023 The Authors

PY - 2023/6

Y1 - 2023/6

N2 - Background: Heterologous 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. Methods: Com-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. Findings: In 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. Interpretation: Heterologous 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.

AB - Background: Heterologous 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. Methods: Com-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. Findings: In 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. Interpretation: Heterologous 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.

KW - Adenovirus vector

KW - Antibody

KW - Heterologous

KW - Persistence

KW - SARS-CoV2

KW - T-cell

KW - Vaccine

KW - mRNA lipid nanoparticle

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U2 - 10.1016/j.jinf.2023.03.027

DO - 10.1016/j.jinf.2023.03.027

M3 - Article

C2 - 37028454

AN - SCOPUS:85153273162

SN - 0163-4453

VL - 86

SP - 574

EP - 583

JO - Journal of Infection

JF - Journal of Infection

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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