Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Merryn VoyseyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKSue Ann Costa ClemensInstitute of Global Health, University of Siena, Siena, Brazil; Department of Paediatrics, University of Oxford, Oxford, UKShabir A. MadhiMRC Vaccines and Infectious Diseases Analytics Research Unit, Johannesburg, South AfricaLily Yin WeckxDepartment of Pediatrics, Universidade Federal de São Paulo, São Paulo, BrazilPedro M. FolegattiJenner Institute, Nuffield Department of Medicine, University of Oxford, UKParvinder K. AleyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKBrian AngusJenner Institute, Nuffield Department of Medicine, University of Oxford, UKVicky L. BaillieRespiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South AfricaShaun BarnabasFamily Centre for Research with Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South AfricaQasim BhoratSoweto Clinical Trials Centre, Soweto, South AfricaSagida BibiOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKCarmen BrinerPerinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaPaola CicconiJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAndrea M. CollinsDepartment of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKRachel Colin-JonesOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKClare CutlandRespiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South AfricaThomas C. DartonDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKKeertan DhedaDivision of Pulmonology, Groote Schuur Hospital and the University of Cape Town, South Africa; Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UKC.J. DuncanDepartment of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle upon Tyne, UKKatherine R. W. EmaryOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKKatie EwerJenner Institute, Nuffield Department of Medicine, University of Oxford, UKLee FairlieWits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaSaul N. FaustNIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UKShuo FengOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKDaniela M. FerreiraDepartment of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKAdam FinnSchool of Population Health Sciences, University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UKAnna L. GoodmanDepartment of Infection, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK; MRC Clinical Trials Unit, University College London, London, UKCatherine GreenClinical BioManufacturing Facility, University of Oxford, Oxford, UKChristopher GreenClinical BioManufacturing Facility, University of Oxford, Oxford, UKPaul T. HeathSt George's Vaccine Institute, St George's, University of London, London, UKCatherine HillWits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaHelen HillDepartment of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKIan HirschAstraZeneca BioPharmaceuticals, Cambridge, UKSusanne H. HodgsonJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAlane IzuVIDA-Vaccines and Infectious Diseases Analytical Research Unit, Johannesburg, South AfricaSusan JacksonJenner Institute, Nuffield Department of Medicine, University of Oxford, UKDaniel JenkinJenner Institute, Nuffield Department of Medicine, University of Oxford, UKCarina C. D. JoeJenner InstituteSimon KerridgeOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKAnthonet KoenVIDA-Vaccines and Infectious Diseases Analytical Research Unit, Johannesburg, South AfricaGaurav KwatraWits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaRajeka LazarusSevern Pathology, North Bristol NHS Trust, Bristol, UKAlison M. LawrieJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAlice LelliottOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKVincenzo LibriNIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, London, UKPatrick LillieDepartment of Infection, Hull University Teaching Hospitals NHS Trust, UKRaburn M. MalloryAstraZeneca BioPharmaceuticals, Cambridge, UKAna Verena Almeida MendesEscola Bahiana de Medicina e Saúde Pública, Salvador, Braziland Hospital São Rafael, Salvador, Brazil; Instituto D'Or, Salvador, BrazilEveline Pı́polo MilanDepartment of Infectious Diseases, Universidade Federal do Rio Grande do Norte, Natal, BrazilAngela M. MinassianJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAlastair McGregorLondon Northwest University Healthcare, Harrow, UKHazel MorrisonJenner Institute, Nuffield Department of Medicine, University of Oxford, UKYama F MujadidiOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKAnusha NanaPerinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaPeter O’ReillyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKSherman D. PadayacheeSetshaba Research Centre, Pretoria, South AfricaAna Maria PittellaDepartment of Internal Medicine, Hospital Quinta D'Or, Rio de Janeiro, Brazil; Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil; Department of Internal Medicine, Universidade UNIGRANRIO, Rio de Janeiro, BrazilEmma PlestedOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKKatrina M. PollockNIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKMaheshi RamasamyOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKSarah RheadOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKAlexandre Vargas SchwarzboldClinical Research Unit, Department of Clinical Medicine, Universidade Federal de Santa Maria, Santa Maria, BrazilNisha SinghOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKDarren SmithCollege of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, UKRinn SongOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USAMatthew D. SnapeOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UKEduardo SprinzInfectious Diseases Service, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilRebecca SutherlandClinical Infection Research Group, Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UKRichard TarrantClinical BioManufacturing Facility, University of Oxford, Oxford, UKEmma C. ThomsonMRC-University of Glasgow Centre for Virus Research & Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UKM. Estée TörökDepartment of Medicine, University of Cambridge, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKMark ToshnerHeart Lung Research Institute, Department of Medicine, University of Cambridge and Royal Papworth Hospital NHS Foundation Trust, Cambridge, UKDavid P. J. TurnerUniversity of Nottingham and Nottingham University Hospitals NHS Trust, UKJohan VekemansAstraZeneca BioPharmaceuticals, Cambridge, UKTonya VillafanaAstraZeneca BioPharmaceuticals, Cambridge, UKMarion WatsonJenner Institute, Nuffield Department of Medicine, University of Oxford, UKChristopher J. WilliamsPublic Health Wales, Cardiff, Wales; Aneurin Bevan University Health Board, Newport, UKAlexander D. DouglasJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAdrian V. S. HillJenner Institute, Nuffield Department of Medicine, University of Oxford, UKTeresa LambeJenner Institute, Nuffield Department of Medicine, University of Oxford, UKSarah C. GilbertJenner Institute, Nuffield Department of Medicine, University of Oxford, UKAndrew J. PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. Electronic address: [email protected]Marites AbanFatola AbayomiKushala W.M. AbeyskeraJeremy AboagyeMatthew AdamKirsty AdamsJames P. AdamsonYemi AdelajaGbadebo AdewetanSyed AdlouKhatija AhmedYasmeen AkhalwayaSaajida AkhalwayaAndrew AlcockL Goodman); NIHR/Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK (Aabidah AliUniversity of London, London, UKElizabeth AllenLauren AllenThamires C. D. S. C Almeida
2020en
ABI
Аннотация
BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
Перевод пока недоступен
Идентификаторы
Цитирования и источники
Цитирований: 3Использованных источников: 0