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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, Greenland, Melanie, Stuart, Arabella, Aley, Parvinder, Andrews, Nick, Cameron, Claire, Charlton, Sue, Clutterbuck, Elizabeth, Collins, Andrea ORCID:, Darton, Tom, Dinesh, Tanya, Duncan, Christopher, Faust, Saul, Ferreira, Daniela ORCID:, Finn, Adam, Goodman, Anna, Green, Christopher, Hallis, Bassam, Heath, Paul, Hill, Helen, Lambe, Teresa, Libri, Vincenzo, Lillie, Patrick, Morey, Ella, Mujadidi, Yama, Payne, Ruth, Plested, Emma, Provstgaard-Morys, Samuel, Ramasamy, Maheshi, Mary Ramsay, Ffph, Read, Robert, Robinson, Hannah, Screaton, Gavin, Singh, Nisha, Turner, David, Turner, Paul, White, Rachel, Nguyen-Van-Tam, Jonathan, Liu, Xinxue and Snape, Matthew (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, Vol 86, Issue 6, pp. 574-583.

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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.

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.

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: 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 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.

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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 18 Apr 2023 09:22
Last Modified: 19 May 2023 13:26


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