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Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.
Barrett, Jordan R; Belij-Rammerstorfer, Sandra; Dold, Christina; Ewer, Katie J; Folegatti, Pedro M; Gilbride, Ciaran; Halkerston, Rachel; Hill, Jennifer; Jenkin, Daniel; Stockdale, Lisa; Verheul, Marije K; Aley, Parvinder K; Angus, Brian; Bellamy, Duncan; Berrie, Eleanor; Bibi, Sagida; Bittaye, Mustapha; Carroll, Miles W; Cavell, Breeze; Clutterbuck, Elizabeth A; Edwards, Nick; Flaxman, Amy; Fuskova, Michelle; Gorringe, Andrew; Hallis, Bassam; Kerridge, Simon; Lawrie, Alison M; Linder, Aline; Liu, Xinxue; Madhavan, Meera; Makinson, Rebecca; Mellors, Jack; Minassian, Angela; Moore, Maria; Mujadidi, Yama; Plested, Emma; Poulton, Ian; Ramasamy, Maheshi N; Robinson, Hannah; Rollier, Christine S; Song, Rinn; Snape, Matthew D; Tarrant, Richard; Taylor, Stephen; Thomas, Kelly M; Voysey, Merryn; Watson, Marion E E; Wright, Daniel; Douglas, Alexander D; Green, Catherine M.
  • Barrett JR; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Belij-Rammerstorfer S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dold C; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Ewer KJ; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Folegatti PM; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Gilbride C; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Halkerston R; Public Health England, Salisbury, UK.
  • Hill J; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Jenkin D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. Daniel.Jenkin@ndm.ox.ac.uk.
  • Stockdale L; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Verheul MK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Aley PK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Angus B; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Bellamy D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Berrie E; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Bibi S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Bittaye M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Carroll MW; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Cavell B; Public Health England, Salisbury, UK.
  • Clutterbuck EA; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Edwards N; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Flaxman A; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Fuskova M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Gorringe A; Public Health England, Salisbury, UK.
  • Hallis B; Public Health England, Salisbury, UK.
  • Kerridge S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Lawrie AM; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Linder A; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Liu X; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Madhavan M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Makinson R; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Mellors J; Public Health England, Salisbury, UK.
  • Minassian A; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Moore M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Mujadidi Y; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Plested E; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Poulton I; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ramasamy MN; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Robinson H; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Rollier CS; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Song R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Snape MD; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Tarrant R; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Taylor S; Public Health England, Salisbury, UK.
  • Thomas KM; Public Health England, Salisbury, UK.
  • Voysey M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Watson MEE; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Wright D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Douglas AD; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Green CM; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Med ; 27(2): 279-288, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065913
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunization, Secondary / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibody Formation Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Humans / Middle aged / Young adult Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-020-01179-4

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunization, Secondary / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibody Formation Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Humans / Middle aged / Young adult Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2021 Document Type: Article Affiliation country: S41591-020-01179-4