| Title: |
Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial |
| Authors: |
Stuart, Arabella S V; Shaw, Robert H; Liu, Xinxue; Greenland, Melanie; Aley, Parvinder K; Andrews, Nick J; Cameron, J. C.; Charlton, Sue; Clutterbuck, Elizabeth A; Collins, Andrea M; Darton, Tom; Dinesh, Tanya; Duncan, Christopher J A; England, Anna; Faust, Saul N; Ferreira, Daniela M; Finn, Adam; Goodman, Anna L; Green, Christopher A; Hallis, Bassam; Heath, Paul T; Hill, Helen; Horsington, Bryn M; Lambe, Teresa; Lazarus, Rajeka; Libri, Vincenzo; Lillie, Patrick J; Mujadidi, Yama F; Payne, Ruth; Plested, Emma L; Provstgaard-Morys, Samuel; Ramasamy, Maheshi N; Ramsay, Mary; Read, Robert C; Robinson, Hannah; Screaton, Gavin R; Singh, Nisha; Turner, David P.J.; Turner, Paul J; Vichos, Iason; White, Rachel; Nguyen-Van-Tam, Jonathan S.; Snape, Matthew D |
| Publisher Information: |
Elsevier |
| Publication Year: |
2021 |
| Collection: |
University of Nottingham: Repository@Nottingham |
| Subject Terms: |
General Medicine |
| Description: |
Background: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). Methods: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. Findings: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://nottingham-repository.worktribe.com/output/7057628; The Lancet; Volume 399; Issue 10319; Pagination 36-49 |
| DOI: |
10.1016/S0140-6736%2821%2902718-5 |
| DOI: |
10.1016/S0140-6736(21)02718-5 |
| Availability: |
https://doi.org/10.1016/S0140-6736%2821%2902718-5; https://nottingham-repository.worktribe.com/file/7057628/1/Stuart%20Lancet%202021; https://nottingham-repository.worktribe.com/output/7057628; https://doi.org/10.1016/S0140-6736(21)02718-5 |
| Rights: |
openAccess ; https://creativecommons.org/licenses/by-nc-sa/3.0/igo/ |
| Accession Number: |
edsbas.B2C3F57 |
| Database: |
BASE |