Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Type Journal Article Author Jordan R. Barrett Author Sandra Belij-Rammerstorfer Author Christina Dold Author Katie J. Ewer Author Pedro M. Folegatti Author Ciaran Gilbride Author Rachel Halkerston Author Jennifer Hill Author Daniel Jenkin Author Lisa Stockdale Author Marije K. Verheul Author Parvinder K. Aley Author Brian Angus Author Duncan Bellamy Author Eleanor Berrie Author Sagida Bibi Author Mustapha Bittaye Author Miles W. Carroll Author Breeze Cavell Author Elizabeth A. Clutterbuck Author Nick Edwards Author Amy Flaxman Author Michelle Fuskova Author Andrew Gorringe Author Bassam Hallis Author Simon Kerridge Author Alison M. Lawrie Author Aline Linder Author Xinxue Liu Author Meera Madhavan Author Rebecca Makinson Author Jack Mellors Author Angela Minassian Author Maria Moore Author Yama Mujadidi Author Emma Plested Author Ian Poulton Author Maheshi N. Ramasamy Author Hannah Robinson Author Christine S. Rollier Author Rinn Song Author Matthew D. Snape Author Richard Tarrant Author Stephen Taylor Author Kelly M. Thomas Author Merryn Voysey Author Marion E. E. Watson Author Daniel Wright Author Alexander D. Douglas Author Catherine M. Green Author Adrian V. S. Hill Author Teresa Lambe Author Sarah Gilbert Author Andrew J. Pollard URL https://www.nature.com/articles/s41591-020-01179-4 Rights 2020 The Author(s), under exclusive licence to Springer Nature America, Inc. Volume 27 Issue 2 Pages 279-288 Publication Nature Medicine ISSN 1546-170X Date 17/12/2020 Extra Bandiera_abtest: a Cg_type: Nature Research Journals Number: 2 Primary_atype: Research Publisher: Nature Publishing Group Subject_term: Randomized controlled trials;Vaccines;Viral infection Subject_term_id: randomized-controlled-trials;vaccines;viral-infection Journal Abbr Nat Med DOI 10.1038/s41591-020-01179-4 Library Catalog www.nature.com Language en Abstract More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18–55 years (NCT04324606). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.