Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine,Cell

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Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine
Cell ( IF 64.5 ) Pub Date : 2021-10-16 , DOI: 10.1016/j.cell.2021.10.011
Rebecca P Payne ₁ , Stephanie Longet ₂ , James A Austin ₃ , Donal T Skelly ₄ , Wanwisa Dejnirattisai ₂ , Sandra Adele ₅ , Naomi Meardon ₆ , Sian Faustini ₇ , Saly Al-Taei ₇ , Shona C Moore ₃ , Tom Tipton ₂ , Luisa M Hering ₃ , Adrienn Angyal ₈ , Rebecca Brown ₈ , Alexander R Nicols ₁ , Natalie Gillson ₉ , Susan L Dobson ₃ , Ali Amini ₁₀ , Piyada Supasa ₂ , Andrew Cross ₁₁ , Alice Bridges-Webb ₁₂ , Laura Silva Reyes ₁₂ , Aline Linder ₁₂ , Gurjinder Sandhar ₈ , Jonathan A Kilby ₈ , Jessica K Tyerman ₁ , Thomas Altmann ₁₃ , Hailey Hornsby ₈ , Rachel Whitham ₆ , Eloise Phillips ₅ , Tom Malone ₅ , Alexander Hargreaves ₂ , Adrian Shields ₁₄ , Ayoub Saei ₉ , Sarah Foulkes ₉ , Lizzie Stafford ₁₅ , Sile Johnson ₁₆ , Daniel G Wootton ₁₇ , Christopher P Conlon ₁₈ , Katie Jeffery ₁₉ , Philippa C Matthews ₂₀ , John Frater ₂₀ , Alexandra S Deeks ₂₀ , Andrew J Pollard ₂₁ , Anthony Brown ₅ , Sarah L Rowland-Jones ₂₂ , Juthathip Mongkolsapaya ₂₃ , Eleanor Barnes ₂₄ , Susan Hopkins ₂₅ , Victoria Hall ₂₆ , Christina Dold ₂₁ , Christopher J A Duncan ₂₇ , Alex Richter ₁₄ , Miles Carroll ₂ , Gavin Screaton ₂ , Thushan I de Silva ₂₂ , Lance Turtle ₂₈ , Paul Klenerman ₂₄ , Susanna Dunachie ₂₉ ,

Affiliation

Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Institute of Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Public Health England, Colindale, London, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK; Great North Children's Hospital, Newcastle, UK.
Institute of Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford University Medical School, Medical Sciences Division, University of Oxford, Oxford, UK.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford Centre For Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Public Health England, Colindale, London, UK; Faculty of Medicine, Department of Infectious Disease, Imperial College London, London, UK; NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK.
Public Health England, Colindale, London, UK; NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK.
Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK; Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford Centre For Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4⁺ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

中文翻译：

BNT162b2 mRNA 疫苗标准给药间隔和延长给药间隔的免疫原性

英国延长了 BNT162b2 mRNA 疫苗的疫苗剂量间隔，以加快单剂量的人群覆盖率。目前，缺乏试验数据，我们在一项针对英国医护人员的研究中解决了这个问题。第一剂疫苗在几周内诱导了对循环 α (B.1.1.7) 变体感染的保护。在一项对 589 名个体进行的亚研究中，我们发现这种单剂量可诱导严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 中和抗体 (NAb) 反应以及对刺突蛋白的持续 B 和 T 细胞反应。与传统的 3 至 4 周方案相比，延长给药间隔（6-14 周）后，NAb 水平更高，同时表达白细胞介素 2 (IL-2)的 CD4 ^{+ T 细胞富集。}先前的 SARS-CoV-2 感染放大并加速了反应。这些关于动态细胞和体液反应的数据表明，延长给药间隔是一种有效的免疫原性方案。

更新日期：2021-11-11

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