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
<strong>Background<br></strong> 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2023
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| _version_ | 1797110446834057216 |
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| author | Shaw, RH Greenland, M Stuart, AS Aley, PK Andrews, NJ Cameron, JC Charlton, S Clutterbuck, EA Collins, AM Darton, T Dinesh, T Duncan, CJ Faust, SN Ferreira, DM Finn, A Goodman, AL Green, CA Hallis, B Heath, PT Hill, H Lambe, T Libri, V Lillie, PJ Morey, E Mujadidi, YF Payne, R Plested, EL Provstgaard-Morys, S Ramasamy, MN Mary Ramsay, F Read, RC Hannah Robinson, RN Screaton, GR Singh, N Turner, DP Turner, PJ Rachel White, RN Nguyen-Van-Tam, JS Liu, X Snape, MD |
| author2 | Com-COV2 Study Group |
| author_facet | Com-COV2 Study Group Shaw, RH Greenland, M Stuart, AS Aley, PK Andrews, NJ Cameron, JC Charlton, S Clutterbuck, EA Collins, AM Darton, T Dinesh, T Duncan, CJ Faust, SN Ferreira, DM Finn, A Goodman, AL Green, CA Hallis, B Heath, PT Hill, H Lambe, T Libri, V Lillie, PJ Morey, E Mujadidi, YF Payne, R Plested, EL Provstgaard-Morys, S Ramasamy, MN Mary Ramsay, F Read, RC Hannah Robinson, RN Screaton, GR Singh, N Turner, DP Turner, PJ Rachel White, RN Nguyen-Van-Tam, JS Liu, X Snape, MD |
| author_sort | Shaw, RH |
| collection | OXFORD |
| description | <strong>Background<br></strong>
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.
<br><strong>Methods<br></strong>
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.
<br><strong>Findings<br></strong>
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).<br>
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.<br>
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.<br><strong>
Interpretation<br></strong>
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. <br>ISRCTN:27841311 EudraCT:2021-001275-16. |
| first_indexed | 2024-03-07T07:54:59Z |
| format | Journal article |
| id | oxford-uuid:bcc82eea-20e2-4846-a8a1-68083bb0e886 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:54:59Z |
| publishDate | 2023 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:bcc82eea-20e2-4846-a8a1-68083bb0e8862023-08-09T14:05:29ZPersistence 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 vaccinesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bcc82eea-20e2-4846-a8a1-68083bb0e886EnglishSymplectic ElementsElsevier2023Shaw, RHGreenland, MStuart, ASAley, PKAndrews, NJCameron, JCCharlton, SClutterbuck, EACollins, AMDarton, TDinesh, TDuncan, CJFaust, SNFerreira, DMFinn, AGoodman, ALGreen, CAHallis, BHeath, PTHill, HLambe, TLibri, VLillie, PJMorey, EMujadidi, YFPayne, RPlested, ELProvstgaard-Morys, SRamasamy, MNMary Ramsay, FRead, RCHannah Robinson, RNScreaton, GRSingh, NTurner, DPTurner, PJRachel White, RNNguyen-Van-Tam, JSLiu, XSnape, MDCom-COV2 Study Group<strong>Background<br></strong> 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. <br><strong>Methods<br></strong> 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. <br><strong>Findings<br></strong> 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).<br> 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.<br> 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.<br><strong> Interpretation<br></strong> 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. <br>ISRCTN:27841311 EudraCT:2021-001275-16. |
| spellingShingle | Shaw, RH Greenland, M Stuart, AS Aley, PK Andrews, NJ Cameron, JC Charlton, S Clutterbuck, EA Collins, AM Darton, T Dinesh, T Duncan, CJ Faust, SN Ferreira, DM Finn, A Goodman, AL Green, CA Hallis, B Heath, PT Hill, H Lambe, T Libri, V Lillie, PJ Morey, E Mujadidi, YF Payne, R Plested, EL Provstgaard-Morys, S Ramasamy, MN Mary Ramsay, F Read, RC Hannah Robinson, RN Screaton, GR Singh, N Turner, DP Turner, PJ Rachel White, RN Nguyen-Van-Tam, JS Liu, X Snape, MD 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 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
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