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

Type Journal Article Author Merryn Voysey Author Sue Ann Costa Clemens Author Shabir A. Madhi Author Lily Y. Weckx Author Pedro M. Folegatti Author Parvinder K. Aley Author Brian Angus Author Vicky L. Baillie Author Shaun L. Barnabas Author Qasim E. Bhorat Author Sagida Bibi Author Carmen Briner Author Paola Cicconi Author Andrea M. Collins Author Rachel Colin-Jones Author Clare L. Cutland Author Thomas C. Darton Author Keertan Dheda Author Christopher J. A. Duncan Author Katherine R. W. Emary Author Katie J. Ewer Author Lee Fairlie Author Saul N. Faust Author Shuo Feng Author Daniela M. Ferreira Author Adam Finn Author Anna L. Goodman Author Catherine M. Green Author Christopher A. Green Author Paul T. Heath Author Catherine Hill Author Helen Hill Author Ian Hirsch Author Susanne H. C. Hodgson Author Alane Izu Author Susan Jackson Author Daniel Jenkin Author Carina C. D. Joe Author Simon Kerridge Author Anthonet Koen Author Gaurav Kwatra Author Rajeka Lazarus Author Alison M. Lawrie Author Alice Lelliott Author Vincenzo Libri Author Patrick J. Lillie Author Raburn Mallory Author Ana V. A. Mendes Author Eveline P. Milan Author Angela M. Minassian Author Alastair McGregor Author Hazel Morrison Author Yama F. Mujadidi Author Anusha Nana Author Peter J. O’Reilly Author Sherman D. Padayachee Author Ana Pittella Author Emma Plested Author Katrina M. Pollock Author Maheshi N. Ramasamy Author Sarah Rhead Author Alexandre V. Schwarzbold Author Nisha Singh Author Andrew Smith Author Rinn Song Author Matthew D. Snape Author Eduardo Sprinz Author Rebecca K. Sutherland Author Richard Tarrant Author Emma C. Thomson Author M. Estée Török Author Mark Toshner Author David P. J. Turner Author Johan Vekemans Author Tonya L. Villafana Author Marion E. E. Watson Author Christopher J. Williams Author Alexander D. Douglas Author Adrian V. S. Hill Author Teresa Lambe Author Sarah C. Gilbert Author Andrew J. Pollard Author Marites Aban Author Fatola Abayomi Author Kushala Abeyskera Author Jeremy Aboagye Author Matthew Adam Author Kirsty Adams Author James Adamson Author Yemi A. Adelaja Author Syed Adlou Author Khatija Ahmed Author Yasmeen Akhalwaya Author Saajida Akhalwaya Author Andrew Alcock Author Aabidah Ali Author Elizabeth R. Allen Author Lauren Allen Author Thamires C. D. S. C. Almeida Author Mariana P. S. Alves Author Fabio Amorim Author Foteini Andritsou Author Rachel Anslow Author Matthew Appleby Author Edward H. Arbe-Barnes Author Mark P. Ariaans Author Beatriz Arns Author Laiana Arruda Author Gbadebo Awedetan Author Paula Azi Author Lorena Azi Author Gavin Babbage Author Catherine Bailey Author Kenneth F. Baker Author Megan Baker Author Natalie Baker Author Philip Baker Author Lisa Baldwin Author Ioana Baleanu Author Danieli Bandeira Author Anna Bara Author Marcella A. S. Barbosa Author Debbie Barker Author Gavin D. Barlow Author Eleanor Barnes Author Andrew S. Barr Author Jordan R. Barrett Author Jessica Barrett Author Louise Bates Author Alexander Batten Author Kirsten Beadon Author Emily Beales Author Rebecca Beckley Author Sandra Belij-Rammerstorfer Author Jonathan Bell Author Duncan Bellamy Author Nancy Bellei Author Sue Belton Author Adam Berg Author Laura Bermejo Author Eleanor Berrie Author Lisa Berry Author Daniella Berzenyi Author Amy Beveridge Author Kevin R. Bewley Author Helen Bexhell Author Sutika Bhikha Author Asad E. Bhorat Author Zaheda E. Bhorat Author Else Bijker Author Geeta Birch Author Sarah Birch Author Adam Bird Author Olivia Bird Author Karen Bisnauthsing Author Mustapha Bittaye Author Katherine Blackstone Author Luke Blackwell Author Heather Bletchly Author Caitlin L. Blundell Author Susannah R. Blundell Author Pritesh Bodalia Author Bruno C. Boettger Author Emma Bolam Author Elena Boland Author Daan Bormans Author Nicola Borthwick Author Francesca Bowring Author Amy Boyd Author Penny Bradley Author Tanja Brenner Author Phillip Brown Author Claire Brown Author Charlie Brown-O'Sullivan Author Scott Bruce Author Emily Brunt Author Ruaridh Buchan Author William Budd Author Yusuf A. Bulbulia Author Melanie Bull Author Jamie Burbage Author Hassan Burhan Author Aileen Burn Author Karen R. Buttigieg Author Nicholas Byard Author Ingrid Cabera Puig Author Gloria Calderon Author Anna Calvert Author Susana Camara Author Michelangelo Cao Author Federica Cappuccini Author João R. Cardoso Author Melanie Carr Author Miles W. Carroll Author Andrew Carson-Stevens Author Yasmin de M. Carvalho Author José A. M. Carvalho Author Helen R. Casey Author Paul Cashen Author Thais Castro Author Lucia Carratala Castro Author Katrina Cathie Author Ana Cavey Author José Cerbino-Neto Author Jim Chadwick Author David Chapman Author Sue Charlton Author Irina Chelysheva Author Oliver Chester Author Sunder Chita Author Jee-Sun Cho Author Liliana Cifuentes Author Elizabeth Clark Author Matthew Clark Author Andrea Clarke Author Elizabeth A. Clutterbuck Author Sarah L. K. Collins Author Christopher P. Conlon Author Sean Connarty Author Naomi Coombes Author Cushla Cooper Author Rachel Cooper Author Lynne Cornelissen Author Tumena Corrah Author Catherine Cosgrove Author Tony Cox Author Wendy E. M. Crocker Author Sarah Crosbie Author Lorraine Cullen Author Dan Cullen Author Debora R. M. F. Cunha Author Christina Cunningham Author Fiona C. Cuthbertson Author Suzete N. Farias Da Guarda Author Larissa P. da Silva Author Brad E. Damratoski Author Zsofia Danos Author Maria T. D. C. Dantas Author Paula Darroch Author Mehreen S. Datoo Author Chandrabali Datta Author Malika Davids Author Sarah L. Davies Author Hannah Davies Author Elizabeth Davis Author Judith Davis Author John Davis Author Maristela M. D. De Nobrega Author Lis Moreno De Oliveira Kalid Author David Dearlove Author Tesfaye Demissie Author Amisha Desai Author Stefania Di Marco Author Claudio Di Maso Author Maria I. S. Dinelli Author Tanya Dinesh Author Claire Docksey Author Christina Dold Author Tao Dong Author Francesca R. Donnellan Author Tannyth Dos Santos Author Thainá G. dos Santos Author Erika Pachecho Dos Santos Author Naomi Douglas Author Charlotte Downing Author Jonathan Drake Author Rachael Drake-Brockman Author Kimberley Driver Author Ruth Drury Author Susanna J. Dunachie Author Benjamin S. Durham Author Lidiana Dutra Author Nicholas J. W. Easom Author Samual van Eck Author Mandy Edwards Author Nick J. Edwards Author Omar M. El Muhanna Author Sean C. Elias Author Mike Elmore Author Marcus English Author Alisgair Esmail Author Yakub Moosa Essack Author Eoghan Farmer Author Mutjaba Farooq Author Madi Farrar Author Leonard Farrugia Author Beverley Faulkner Author Sofiya Fedosyuk Author Sally Felle Author Shuo Feng Author Carla Ferreira Da Silva Author Samantha Field Author Richard Fisher Author Amy Flaxman Author James Fletcher Author Hazel Fofie Author Henry Fok Author Karen J. Ford Author Jamie Fowler Author Pedro H. A. Fraiman Author Emma Francis Author Marilia M. Franco Author John Frater Author Marilúcia S. M. Freire Author Samantha H. Fry Author Sabrina Fudge Author Julie Furze Author Michelle Fuskova Author Pablo Galian-Rubio Author Eva Galiza Author Harriet Garlant Author Madita Gavrila Author Ailsa Geddes Author Karyna A. Gibbons Author Ciaran Gilbride Author Hardeep Gill Author Sharon Glynn Author Kerry Godwin Author Karishma Gokani Author Ursula Carvalho Goldoni Author Maria Goncalves Author Isabela G. S. Gonzalez Author Jayne Goodwin Author Amina Goondiwala Author Katherine Gordon-Quayle Author Giacomo Gorini Author Janet Grab Author Lara Gracie Author Melanie Greenland Author Nicola Greenwood Author Johann Greffrath Author Marisa M. Groenewald Author Leonardo Grossi Author Gaurav Gupta Author Mark Hackett Author Bassam Hallis Author Mainga Hamaluba Author Elizabeth Hamilton Author Daniel Hammersley Author Aidan T. Hanrath Author Brama Hanumunthadu Author Stephanie A. Harris Author Clair Harris Author Tara Harris Author Thomas D. Harrison Author Daisy Harrison Author Thomas C. Hart Author Birgit Hartnell Author Shadin Hassan Author John Haughney Author Sophia Hawkins Author Jodie Hay Author Ian Head Author John Henry Author Macarena Hermosin Herrera Author David B. Hettle Author Jennifer Hill Author Gina Hodges Author Elizea Horne Author Mimi M. Hou Author Catherine Houlihan Author Elizabeth Howe Author Nicola Howell Author Jonathan Humphreys Author Holly E. Humphries Author Katrina Hurley Author Claire Huson Author Angela Hyder-Wright Author Catherine Hyamns Author Sabina Ikram Author Alka Ishwarbhai Author Monica Ivan Author Poppy Iveson Author Vidyashankara Iyer Author Frederic Jackson Author Jeanne De Jager Author Shameem Jaumdally Author Helen Jeffers Author Natasha Jesudason Author Bryony Jones Author Kathryn Jones Author Elizabeth Jones Author Christopher Jones Author Marianna Rocha Jorge Author Aylin Jose Author Amar Joshi Author Eduardo A. M. S. Júnior Author Joanne Kadziola Author Reshma Kailath Author Faeeza Kana Author Konstantinos Karampatsas Author Mwila Kasanyinga Author Jade Keen Author Elizabeth J. Kelly Author Dearbhla M. Kelly Author Debbie Kelly Author Sarah Kelly Author David Kerr Author Renato de Ávila Kfouri Author Liaquat Khan Author Baktash Khozoee Author Sarah Kidd Author Annabel Killen Author Jasmin Kinch Author Patrick Kinch Author Lloyd D. W. King Author Thomas B. King Author Lucy Kingham Author Paul Klenerman Author Francesca Knapper Author Julian C. Knight Author Daniel Knott Author Stanislava Koleva Author Matilda Lang Author Gail Lang Author Colin W. Larkworthy Author Jessica P. J. Larwood Author Rebecca Law Author Erica M. Lazarus Author Amanda Leach Author Emily A. Lees Author Nana-Marie Lemm Author Alvaro Lessa Author Stephanie Leung Author Yuanyuan Li Author Amelia M. Lias Author Kostas Liatsikos Author Aline Linder Author Samuel Lipworth Author Shuchang Liu Author Xinxue Liu Author Adam Lloyd Author Stephanie Lloyd Author Lisa Loew Author Raquel Lopez Ramon Author Leandro Lora Author Vicki Lowthorpe Author Kleber Luz Author Jonathan C. MacDonald Author Gordon MacGregor Author Meera Madhavan Author David O. Mainwaring Author Edson Makambwa Author Rebecca Makinson Author Mookho Malahleha Author Ross Malamatsho Author Garry Mallett Author Kushal Mansatta Author Takalani Maoko Author Katlego Mapetla Author Natalie G. Marchevsky Author Spyridoula Marinou Author Emma Marlow Author Gabriela N. Marques Author Paula Marriott Author Richard P. Marshall Author Julia L. Marshall Author Flávia J. Martins Author Masebole Masenya Author Mduduzi Masilela Author Shauna K. Masters Author Moncy Mathew Author Hosea Matlebjane Author Kedidimetse Matshidiso Author Olga Mazur Author Andrea Mazzella Author Hugh McCaughan Author Joanne McEwan Author Joanna McGlashan Author Lorna McInroy Author Zoe McIntyre Author Daniela McLenaghan Author Nicky McRobert Author Steve McSwiggan Author Clare Megson Author Savviz Mehdipour Author Wilma Meijs Author Renata N. Á Mendonça Author Alexander J. Mentzer Author Neginsadat Mirtorabi Author Celia Mitton Author Sibusiso Mnyakeni Author Fiona Moghaddas Author Kgaogelo Molapo Author Mapule Moloi Author Maria Moore Author M. Isabel Moraes-Pinto Author Marni Moran Author Ella Morey Author Róisín Morgans Author Susan Morris Author Sheila Morris Author Helen C. Morris Author Franca Morselli Author Gertraud Morshead Author Richard Morter Author Lynelle Mottal Author Andrew Moultrie Author Nathifa Moya Author Mushiya Mpelembue Author Sibekezelo Msomi Author Yvonne Mugodi Author Ekta Mukhopadhyay Author Jilly Muller Author Alasdair Munro Author Claire Munro Author Sarah Murphy Author Philomena Mweu Author Celia Hatsuko Myasaki Author Gurudutt Naik Author Kush Naker Author Eleni Nastouli Author Abida Nazir Author Bongani Ndlovu Author Fabio Neffa Author Cecilia Njenga Author Helena Noal Author Andrés Noé Author Gabrielle Novaes Author Fay L. Nugent Author Géssika Nunes Author Katie O'Brien Author Daniel O'Connor Author Miranda Odam Author Suzette Oelofse Author Blanche Oguti Author Victoria Olchawski Author Neil J. Oldfield Author Marianne G. Oliveira Author Catarina Oliveira Author Angela Oosthuizen Author Paula O'Reilly Author Piper Osborne Author David R. J. Owen Author Lydia Owen Author Daniel Owens Author Nelly Owino Author Mihaela Pacurar Author Brenda V. B. Paiva Author Edna M. F. Palhares Author Susan Palmer Author Sivapriyai Parkinson Author Helena M. R. T. Parracho Author Karen Parsons Author Dipak Patel Author Bhumika Patel Author Faeezah Patel Author Kelly Patel Author Maia Patrick-Smith Author Ruth O. Payne Author Yanchun Peng Author Elizabeth J. Penn Author Anna Pennington Author Marco Polo Peralta Alvarez Author James Perring Author Nicola Perry Author Rubeshan Perumal Author Sahir Petkar Author Tricia Philip Author Daniel J. Phillips Author Jennifer Phillips Author Mary Kgomotso Phohu Author Lorinda Pickup Author Sonja Pieterse Author Jo Piper Author Dimitra Pipini Author Mary Plank Author Joan Du Plessis Author Samuel Pollard Author Jennifer Pooley Author Anil Pooran Author Ian Poulton Author Claire Powers Author Fernando B. Presa Author David A. Price Author Vivien Price Author Marcelo Primeira Author Pamela C. Proud Author Samuel Provstgaard-Morys Author Sophie Pueschel Author David Pulido Author Sheena Quaid Author Ria Rabara Author Alexandra Radford Author Kajal Radia Author Durga Rajapaska Author Thurkka Rajeswaran Author Alberto San Francisco Ramos Author Fernando Ramos Lopez Author Tommy Rampling Author Jade Rand Author Helen Ratcliffe Author Tom Rawlinson Author David Rea Author Byron Rees Author Jesús Reiné Author Mila Resuello-Dauti Author Emilia Reyes Pabon Author Carla M. Ribiero Author Marivic Ricamara Author Alex Richter Author Neil Ritchie Author Adam J. Ritchie Author Alexander J. Robbins Author Hannah Roberts Author Ryan E. Robinson Author Hannah Robinson Author Talita T. Rocchetti Author Beatriz Pinho Rocha Author Sophie Roche Author Christine Rollier Author Louisa Rose Author Amy L. Ross Russell Author Lindie Rossouw Author Simon Royal Author Indra Rudiansyah Author Sarah Ruiz Author Stephen Saich Author Claudia Sala Author Jessica Sale Author Ahmed M. Salman Author Natalia Salvador Author Stephannie Salvador Author Milla Sampaio Author Annette D. Samson Author Amada Sanchez-Gonzalez Author Helen Sanders Author Katherine Sanders Author Erika Santos Author Mayara F. S. Santos Guerra Author Iman Satti Author Jack E. Saunders Author Caroline Saunders Author Aakifah Sayed Author Ina Schim van der Loeff Author Annina B. Schmid Author Ella Schofield Author Gavin Screaton Author Samiullah Seddiqi Author Rameswara R. Segireddy Author Roberta Senger Author Sonia Serrano Author Rajiv Shah Author Imam Shaik Author Hannah E. Sharpe Author Katherine Sharrocks Author Robert Shaw Author Adam Shea Author Amy Shepherd Author James G. Shepherd Author Farah Shiham Author Emad Sidhom Author Sarah E. Silk Author Antonio Carlos da Silva Moraes Author Gilberto Silva-Junior Author Laura Silva-Reyes Author Anderson D. Silveira Author Mariana B. V. Silveira Author Jaisi Sinha Author Donal T. Skelly Author Daniel C. Smith Author Nick Smith Author Holly E. Smith Author David J. Smith Author Catherine C. Smith Author Airanuédida Soares Author Tiago Soares Author Carla Solórzano Author Guilherme L. Sorio Author Kim Sorley Author Tiffany Sosa-Rodriguez Author Cinthia M. C. D. L. Souza Author Bruno S. D. F. Souza Author Alessandra R. Souza Author Alexandra J. Spencer Author Fernanda Spina Author Louise Spoors Author Lizzie Stafford Author Imogen Stamford Author Igor Starinskij Author Ricardo Stein Author Jill Steven Author Lisa Stockdale Author Lisa V. Stockwell Author Louise H. Strickland Author Arabella C. Stuart Author Ann Sturdy Author Natalina Sutton Author Anna Szigeti Author Abdessamad Tahiri-Alaoui Author Rachel Tanner Author Carol Taoushanis Author Alexander W. Tarr Author Keja Taylor Author Ursula Taylor Author Iona Jennifer Taylor Author Justin Taylor Author Rebecca te Water Naude Author Yrene Themistocleous Author Andreas Themistocleous Author Merin Thomas Author Kelly Thomas Author Tonia M. Thomas Author Asha Thombrayil Author Fawziyah Thompson Author Amber Thompson Author Kevin Thompson Author Ameeka Thompson Author Julia Thomson Author Viv Thornton-Jones Author Patrick J. Tighe Author Lygia Accioly Tinoco Author Gerlynn Tiongson Author Bonolo Tladinyane Author Michele Tomasicchio Author Adriana Tomic Author Susan Tonks Author Nguyen Tran Author Julia Tree Author Gerry Trillana Author Charlotte Trinham Author Rose Trivett Author Adam Truby Author Betty Lebogang Tsheko Author Aadil Turabi Author Richard Turner Author Cheryl Turner Author Marta Ulaszewska Author Benjamin R. Underwood Author Rachel Varughese Author Dennis Verbart Author Marije Verheul Author Iason Vichos Author Taiane Vieira Author Claire S. Waddington Author Laura Walker Author Erica Wallis Author Matthew Wand Author Deborah Warbick Author Theresa Wardell Author George Warimwe Author Sarah C. Warren Author Bridget Watkins Author Ekaterina Watson Author Stewart Webb Author Alice Webb-Bridges Author Angela Webster Author Jessica Welch Author Jeanette Wells Author Alison West Author Caroline White Author Rachel White Author Paul Williams Author Rachel L. Williams Author Rebecca Winslow Author Mark Woodyer Author Andrew T. Worth Author Danny Wright Author Marzena Wroblewska Author Andy Yao Author Rafael Zimmer Author Dalila Zizi Author Peter Zuidewind URL https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/abstract Publication The Lancet ISSN 0140-6736, 1474-547X Date 08/12/2020 Extra Publisher: Elsevier PMID: 33306989 Journal Abbr The Lancet DOI 10.1016/S0140-6736(20)32661-1 Library Catalog www.thelancet.com Language English Abstract 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 This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 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 Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=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. Short Title Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2