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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

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

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 Thumbnail


Authors

Robert H Shaw

Melanie Greenland

Arabella S V Stuart

Parvinder K Aley

Nick J Andrews

J. Claire Cameron

Sue Charlton

Elizabeth A Clutterbuck

Andrea M Collins

Tom Darton

Tanya Dinesh

Christopher J A Duncan

Saul N Faust

Daniela M Ferreira

Adam Finn

Anna L Goodman

Christopher A Green

Bassam Hallis

Paul T Heath

Helen Hill

Teresa Lambe

Vincenzo Libri

Patrick J Lillie

Ella Morey

Yama F Mujadidi

Ruth Payne

Emma L Plested

Samuel Provstgaard-Morys

Maheshi N Ramasamy

Ffph Mary Ramsay

Robert C Read

R N Hannah Robinson

Gavin R Screaton

Nisha Singh

DAVID TURNER david.turner@nottingham.ac.uk
Clinical Associate Professor

Paul J Turner

Rachel White

Xinxue Liu

Matthew D Snape



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.

Citation

Shaw, R. H., Greenland, M., Stuart, A. S. V., Aley, P. K., Andrews, N. J., Cameron, J. C., …Snape, M. D. (2023). 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. Journal of Infection, 86(6), 574-583. https://doi.org/10.1016/j.jinf.2023.03.027

Journal Article Type Article
Acceptance Date Mar 31, 2023
Online Publication Date Apr 6, 2023
Publication Date 2023-06
Deposit Date Apr 19, 2023
Publicly Available Date Apr 19, 2023
Journal Journal of infection
Print ISSN 0163-4453
Electronic ISSN 1532-2742
Publisher British Infection Association
Peer Reviewed Peer Reviewed
Volume 86
Issue 6
Pages 574-583
DOI https://doi.org/10.1016/j.jinf.2023.03.027
Keywords Protein, Antibody, Vaccine, Adenovirus vector, Vaccination, Persistence, T cell, Adjuvant, Cellular, Humoral, Subgroup, Heterologous, T-cell, immunology, homologous, Tcell, Sars-cov2, Covid, Mrna Lipid Nanoparticle
Public URL https://nottingham-repository.worktribe.com/output/19779082
Publisher URL https://www.journalofinfection.com/article/S0163-4453(23)00199-8/fulltext
Related Public URLs https://www.sciencedirect.com/science/article/pii/S0163445323001998
PMID 37028454

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