| Title: |
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. |
| Authors: |
Voysey, Merryn; Costa Clemens, Sue Ann; Madhi, Shabir A; Weckx, Lily Y; Folegatti, Pedro M; Aley, Parvinder K; Angus, Brian; Baillie, Vicky L; Barnabas, Shaun L; Bhorat, Qasim E; Bibi, Sagida; Briner, Carmen; Cicconi, Paola; Clutterbuck, Elizabeth A; Collins, Andrea M; Cutland, Clare L; Darton, Thomas C; Dheda, Keertan; Dold, Christina; Duncan, Christopher JA; Emary, Katherine RW; Ewer, Katie J; Flaxman, Amy; Fairlie, Lee; Faust, Saul N; Feng, Shuo; Ferreira, Daniela M; Finn, Adam; Galiza, Eva; Goodman, Anna L; Green, Catherine M; Green, Christopher A; Greenland, Melanie; Hill, Catherine; Hill, Helen C; Hirsch, Ian; Izu, Alane; Jenkin, Daniel; Joe, Carina CD; Kerridge, Simon; Koen, Anthonet; Kwatra, Gaurav; Lazarus, Rajeka; Libri, Vincenzo; Lillie, Patrick J; Marchevsky, Natalie G; Marshall, Richard P; Mendes, Ana VA; Milan, Eveline P; Minassian, Angela M; McGregor, Alastair; Mujadidi, Yama F; Nana, Anusha; Padayachee, Sherman D; Phillips, Daniel J; Pittella, Ana; Plested, Emma; Pollock, Katrina M; Ramasamy, Maheshi N; Ritchie, Adam J; Robinson, Hannah; Schwarzbold, Alexandre V; Smith, Andrew; Song, Rinn; Snape, Matthew D; Sprinz, Eduardo; Sutherland, Rebecca K; Thomson, Emma C; Török, M Estée; Toshner, Mark; Turner, David PJ; Vekemans, Johan; Villafana, Tonya L; White, Thomas; Williams, Christopher J; Douglas, Alexander D; Hill, Adrian VS; Lambe, Teresa; Gilbert, Sarah C; Pollard, Andrew J; Oxford COVID Vaccine Trial Group |
| Publisher Information: |
Elsevier; Department of Medicine; //doi.org/10.1016/s0140-6736(21)00432-3 |
| Publication Year: |
2022 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Adolescent; Adult; Aged; Antibody Formation; Asymptomatic Infections; COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Humans; Immunization Schedule; Immunization; Secondary; Middle Aged; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult |
| Description: |
BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/334441 |
| DOI: |
10.17863/CAM.81856 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/334441; https://doi.org/10.17863/CAM.81856 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.79909A0 |
| Database: |
BASE |