TY - JOUR
AU - Shaw, Robert H.
AU - Greenland, Melanie
AU - Stuart, Arabella S.V.
AU - Aley, Parvinder K.
AU - Andrews, Nick
AU - Cameron, J. Claire
AU - Charlton, Sue
AU - Clutterbuck, Elizabeth A.
AU - Collins, Andrea M.
AU - Darton, Thomas C.
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 C.
AU - Lambe, Teresa
AU - Libri, Vincenzo
AU - Lillie, Patrick J.
AU - Morey, Ella
AU - Mujadidi, Yama F.
AU - Payne, Ruth
AU - Plested, Emma
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.
AU - Com-COV2 Study Group
PY - 2023
DA - April
TI - 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
JO - Journal of Infection
DO - https://doi.org/10.1016/j.jinf.2023.03.027
AB - BackgroundHeterologous 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.MethodsCom-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.FindingsIn 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 differentantibody responseto BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels ofneutralising antibodies.InterpretationHeterologous 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.
PB - Elsevier
UR - https://publichealthscotland.scot/id/135644
KW - Coronavirus (COVID-19)
KW - Immunisation and screening
ER