Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Type Journal Article Author Pedro M. Folegatti Author Katie J. Ewer Author Parvinder K. Aley Author Brian Angus Author Stephan Becker Author Sandra Belij-Rammerstorfer Author Duncan Bellamy Author Sagida Bibi Author Mustapha Bittaye Author Elizabeth A. Clutterbuck Author Christina Dold Author Saul N. Faust Author Adam Finn Author Amy L. Flaxman Author Bassam Hallis Author Paul Heath Author Daniel Jenkin Author Rajeka Lazarus Author Rebecca Makinson Author Angela M. Minassian Author Katrina M. Pollock Author Maheshi Ramasamy Author Hannah Robinson Author Matthew Snape Author Richard Tarrant Author Merryn Voysey Author Catherine Green Author Alexander D. Douglas Author Adrian V. S. Hill Author Teresa Lambe Author Sarah C. Gilbert Author Andrew J. Pollard Author Jeremy Aboagye Author Kelly Adams Author Aabidah Ali Author Elizabeth Allen Author Jennifer L. Allison Author Rachel Anslow Author Edward H. Arbe-Barnes Author Gavin Babbage Author Kenneth Baillie Author Megan Baker Author Natalie Baker Author Philip Baker Author Ioana Baleanu Author Juliana Ballaminut Author Eleanor Barnes Author Jordan Barrett Author Louise Bates Author Alexander Batten Author Kirsten Beadon Author Rebecca Beckley Author Eleanor Berrie Author Lisa Berry Author Amy Beveridge Author Kevin R. Bewley Author Else Margreet Bijker Author Tracey Bingham Author Luke Blackwell Author Caitlin L. Blundell Author Emma Bolam Author Elena Boland Author Nicola Borthwick Author Thomas Bower Author Amy Boyd Author Tanja Brenner Author Philip D. Bright Author Charlie Brown-O'Sullivan Author Emily Brunt Author Jamie Burbage Author Sharon Burge Author Karen R. Buttigieg Author Nicholas Byard Author Ingrid Cabera Puig Author Anna Calvert Author Susana Camara Author Michelangelo Cao Author Federica Cappuccini Author Melanie Carr Author Miles W. Carroll Author Victoria Carter Author Katrina Cathie Author Ruth J. Challis Author Sue Charlton Author Irina Chelysheva Author Jee-Sun Cho Author Paola Cicconi Author Liliana Cifuentes Author Helen Clark Author Elizabeth Clark Author Tom Cole Author Rachel Colin-Jones Author Christopher P. Conlon Author Aislinn Cook Author Naomi S. Coombes Author Rachel Cooper Author Catherine A. Cosgrove Author Karen Coy Author Wendy E. M. Crocker Author Christina J. Cunningham Author Brad E. Damratoski Author Lynne Dando Author Mehreen S. Datoo Author Hannah Davies Author Hans De Graaf Author Tesfaye Demissie Author Claudio Di Maso Author Isabelle Dietrich Author Tao Dong Author Francesca R. Donnellan Author Naomi Douglas Author Charlotte Downing Author Jonathan Drake Author Rachael Drake-Brockman Author Ruth Elizabeth Drury Author Susanna Jane Dunachie Author Nick J. Edwards Author Frances D. L. Edwards Author Chris J. Edwards Author Sean C. Elias Author Michael J. Elmore Author Katherine R. W. Emary Author Marcus Rex English Author Susanne Fagerbrink Author Sally Felle Author Shuo Feng Author Samantha Field Author Carine Fixmer Author Clare Fletcher Author Karen J. Ford Author Jamie Fowler Author Polly Fox Author Emma Francis Author John Frater Author Julie Furze Author Michelle Fuskova Author Eva Galiza Author Diane Gbesemete Author Ciaran Gilbride Author Kerry Godwin Author Giacomo Gorini Author Lyndsey Goulston Author Caroline Grabau Author Lara Gracie Author Zoe Gray Author Lucy Belle Guthrie Author Mark Hackett Author Sandro Halwe Author Elizabeth Hamilton Author Joseph Hamlyn Author Brama Hanumunthadu Author Irasha Harding Author Stephanie A. Harris Author Andrew Harris Author Daisy Harrison Author Clare Harrison Author Thomas C. Hart Author Louise Haskell Author Sophia Hawkins Author Ian Head Author John Aaron Henry Author Jennifer Hill Author Susanne H. C. Hodgson Author Mimi M. Hou Author Elizabeth Howe Author Nicola Howell Author Cecilia Hutlin Author Sabina Ikram Author Catherine Isitt Author Poppy Iveson Author Susan Jackson Author Frederic Jackson Author Sir William James Author Megan Jenkins Author Elizabeth Jones Author Kathryn Jones Author Christine E. Jones Author Bryony Jones Author Reshma Kailath Author Konstantinos Karampatsas Author Jade Keen Author Sarah Kelly Author Dearbhla Kelly Author David Kerr Author Simon Kerridge Author Liaquat Khan Author Uzma Khan Author Annabel Killen Author Jasmin Kinch Author Thomas B. King Author Lloyd King Author Jade King Author Lucy Kingham-Page Author Paul Klenerman Author Francesca Knapper Author Julian C. Knight Author Daniel Knott Author Stanislava Koleva Author Alexandra Kupke Author Colin W. Larkworthy Author Jessica P. J. Larwood Author Anna Laskey Author Alison M. Lawrie Author Arlene Lee Author Kim Yee Ngan Lee Author Emily A. Lees Author Helen Legge Author Alice Lelliott Author Nana-Marie Lemm Author Amelia M. Lias Author Aline Linder Author Samuel Lipworth Author Xinxue Liu Author Shuchang Liu Author Raquel Lopez Ramon Author May Lwin Author Francesca Mabesa Author Meera Madhavan Author Garry Mallett Author Kushal Mansatta Author Ines Marcal Author Spyridoula Marinou Author Emma Marlow Author Julia L. Marshall Author Jane Martin Author Joanne McEwan Author Lorna McInroy Author Gretchen Meddaugh Author Alexander J. Mentzer Author Neginsadat Mirtorabi Author Maria Moore Author Edward Moran Author Ella Morey Author Victoria Morgan Author Susan Jane Morris Author Hazel Morrison Author Gertraud Morshead Author Richard Morter Author Yama F. Mujadidi Author Jilly Muller Author Tatiana Munera-Huertas Author Claire Munro Author Alasdair Munro Author Sarah Murphy Author Vincent J. Munster Author Philomena Mweu Author Andrés Noé Author Fay L. Nugent Author Elizabeth Nuthall Author Katie O'Brien Author Daniel O'Connor Author Blanché Oguti Author Jennifer L. Oliver Author Catarina Oliveira Author Peter John O'Reilly Author Mairead Osborn Author Piper Osborne Author Cathy Owen Author Daniel Owens Author Nelly Owino Author Mihaela Pacurar Author Kaye Parker Author Helena Parracho Author Maia Patrick-Smith Author Victoria Payne Author Jennifer Pearce Author Yanchun Peng Author Marco Polo Peralta Alvarez Author James Perring Author Katja Pfafferott Author Dimitra Pipini Author Emma Plested Author Helen Pluess-Hall Author Katrina Pollock Author Ian Poulton Author Laura Presland Author Samuel Provstgaard-Morys Author David Pulido Author Kajal Radia Author Fernando Ramos Lopez Author Jade Rand Author Helen Ratcliffe Author Thomas Rawlinson Author Sarah Rhead Author Amy Riddell Author Adam John Ritchie Author Hannah Roberts Author Joanna Robson Author Sophie Roche Author Cornelius Rohde Author Christine S. Rollier Author Rossana Romani Author Indra Rudiansyah Author Stephen Saich Author Sara Sajjad Author Stephannie Salvador Author Lidia Sanchez Riera Author Helen Sanders Author Katherine Sanders Author Shari Sapaun Author Chloe Sayce Author Ella Schofield Author Gavin Screaton Author Beatrice Selby Author Calum Semple Author Hannah R. Sharpe Author Imam Shaik Author Adam Shea Author Holly Shelton Author Sarah Silk Author Laura Silva-Reyes Author Donal T. Skelly Author Heather Smee Author Catherine C. Smith Author David J. Smith Author Rinn Song Author Alexandra J. Spencer Author Elizabeth Stafford Author Amy Steele Author Elena Stefanova Author Lisa Stockdale Author Anna Szigeti Author Abdessamad Tahiri-Alaoui Author Moira Tait Author Helen Talbot Author Rachel Tanner Author Iona Jennifer Taylor Author Victoria Taylor Author Rebecca Te Water Naude Author Nazia Thakur Author Yrene Themistocleous Author Andreas Themistocleous Author Merin Thomas Author Tonia M. Thomas Author Amber Thompson Author Samantha Thomson-Hill Author Jennifer Tomlins Author Susan Tonks Author James Towner Author Nguyen Tran Author Julia A. Tree Author Adam Truby Author Kate Turkentine Author Cheryl Turner Author Nicola Turner Author Sally Turner Author Toby Tuthill Author Marta Ulaszewska Author Rachel Varughese Author Neeltje Van Doremalen Author Kristin Veighey Author Marije K. Verheul Author Iason Vichos Author Elia Vitale Author Laura Walker Author Marion E. E. Watson Author Benjamin Welham Author Julie Wheat Author Caroline White Author Rachel White Author Andrew T. Worth Author Danny Wright Author Suzie Wright Author Xin Li Yao Author Yasmine Yau URL https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/abstract Volume 396 Issue 10249 Pages 467-478 Publication The Lancet ISSN 0140-6736, 1474-547X Date 20/07/2020 Extra Publisher: Elsevier PMID: 32702298 Journal Abbr The Lancet DOI 10.1016/S0140-6736(20)31604-4 Library Catalog www.thelancet.com Language English Abstract Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). Short Title Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2