Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Rebecca P Payne; Stephanie Longet; James A Austin; Donal T Skelly; Wanwisa Dejnirattisai; Sandra Adele; Naomi Meardon; Sian Faustini; Saly Al-Taei; Shona C Moore; Tom Tipton; Luisa M Hering; Adrienn Angyal; Rebecca Brown; Alexander R Nicols; Natalie Gillson; Susan L Dobson; Ali Amini; Piyada Supasa; Andrew Cross; Alice Bridges-Webb; Laura Silva Reyes; Aline Linder; Gurjinder Sandhar; Jonathan A Kilby; Jessica K Tyerman; Thomas Altmann; Hailey Hornsby; Rachel Whitham; Eloise Phillips; Tom Malone; Alexander Hargreaves; Adrian Shields; Ayoub Saei; Sarah Foulkes; Lizzie Stafford; Sile Johnson; Daniel G Wootton; Christopher P Conlon; Katie Jeffery; Philippa C Matthews; John Frater; Alexandra S Deeks; Andrew J Pollard; Anthony Brown; Sarah L Rowland-Jones; Juthathip Mongkolsapaya; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christina Dold; Christopher J A Duncan; Alex Richter; Miles Carroll; Gavin Screaton; Thushan I de Silva; Lance Turtle; Paul Klenerman; Susanna Dunachie; PITCH Consortium

doi:10.1016/j.cell.2021.10.011

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Cell. 2021 Nov 11;184(23):5699-5714.e11. doi: 10.1016/j.cell.2021.10.011. Epub 2021 Oct 16.

Authors

Rebecca P Payne¹, Stephanie Longet², James A Austin³, Donal T Skelly⁴, Wanwisa Dejnirattisai², Sandra Adele⁵, Naomi Meardon⁶, Sian Faustini⁷, Saly Al-Taei⁷, Shona C Moore³, Tom Tipton², Luisa M Hering³, Adrienn Angyal⁸, Rebecca Brown⁸, Alexander R Nicols⁹, Natalie Gillson¹⁰, Susan L Dobson³, Ali Amini¹¹, Piyada Supasa², Andrew Cross¹², Alice Bridges-Webb¹³, Laura Silva Reyes¹³, Aline Linder¹³, Gurjinder Sandhar⁸, Jonathan A Kilby⁸, Jessica K Tyerman⁹, Thomas Altmann¹⁴, Hailey Hornsby⁸, Rachel Whitham⁶, Eloise Phillips⁵, Tom Malone⁵, Alexander Hargreaves², Adrian Shields¹⁵, Ayoub Saei¹⁰, Sarah Foulkes¹⁰, Lizzie Stafford¹⁶, Sile Johnson¹⁷, Daniel G Wootton¹⁸, Christopher P Conlon¹⁹, Katie Jeffery²⁰, Philippa C Matthews²¹, John Frater²¹, Alexandra S Deeks²¹, Andrew J Pollard²², Anthony Brown⁵, Sarah L Rowland-Jones²³, Juthathip Mongkolsapaya²⁴, Eleanor Barnes²⁵, Susan Hopkins²⁶, Victoria Hall²⁷, Christina Dold²², Christopher J A Duncan²⁸, Alex Richter¹⁵, Miles Carroll², Gavin Screaton², Thushan I de Silva²³, Lance Turtle²⁹, Paul Klenerman³⁰, Susanna Dunachie³¹; PITCH Consortium

Collaborators

PITCH Consortium:
Hibatullah Abuelgasim, Emily Adland, Syed Adlou, Hossain Delowar Akther, Ahmed Alhussni, Mohammad Ali, M Azim Ansari, Carolina V Arancibia-Cárcamo, Martin Bayley, Helen Brown, Jeremy Chalk, Meera Chand, Anu Chawla, Senthil Chinnakannan, Joseph Cutteridge, Catherine de Lara, Lucy Denly, Ben Diffey, Stavros Dimitriadis, Thomas M Drake, Timothy Donnison, Maeva Dupont, David Eyre, Alex Fairman, Siobhan Gardiner, Javier Gilbert-Jarmillo, Philip Goulder, Carl-Philipp Hackstein, Sophie Hambleton, Muzlifah Haniffa, Jenny Haworth, Jennifer Holmes, Emily Horner, Anni Jämsén, Sile Johnson, Chris Jones, Mwila Kasanyinga, Sinead Kelly, Rosemary Kirk, Michael L Knight, Allan Lawrie, Lian Lee, Lauren Lett, Katy Lillie, Nicholas Lim, Hema Mehta, Alexander J Mentzer, Denise O'Donnell, Ane Ogbe, Matthew Pace, Brendan A I Payne, Gareth Platt, Sonia Poolan, Nicholas Provine, Narayan Ramamurthy, Nichola Robinson, Leigh Romaniuk, Patpong Rongkard, Oliver L Sampson, Beatrice Simmons, Jarmila S Spegarova, Emily Stephenson, Kris Subramaniam, James Thaventhiran, Sarah Thomas, Simon Travis, Stephanie Tucker, Helena Turton, Adam Watson, Lisa Watson, Esme Weeks, Robert Wilson, Steven Wood, Rachel Wright, Huiyuan Xiao, Amira A T Zawia

Affiliations

¹ Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK. Electronic address: rebecca.payne2@newcastle.ac.uk.
² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
⁴ 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.
⁵ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
⁶ Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁷ Institute of Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK.
⁸ Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
⁹ Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK.
¹⁰ Public Health England, Colindale, London, UK.
¹¹ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
¹² Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
¹³ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁴ Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, Newcastle, UK; Great North Children's Hospital, Newcastle, UK.
¹⁵ Institute of Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹⁶ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹⁷ 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.
¹⁸ 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.
¹⁹ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford Centre For Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
²⁰ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²¹ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
²² Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
²³ Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
²⁴ 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.
²⁵ 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.
²⁶ 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.
²⁷ Public Health England, Colindale, London, UK; NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK.
²⁸ 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.
²⁹ 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.
³⁰ 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. Electronic address: paul.klenerman@ndm.ox.ac.uk.
³¹ 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.

Abstract

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.

Keywords: B cell; BNT162b2; COVID-19; SARS-CoV-2; T cell; antibody; dosing interval; neutralization; vaccine; variants of concern.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
BNT162 Vaccine
COVID-19 / blood
COVID-19 / immunology
COVID-19 / virology
COVID-19 Vaccines / immunology*
Cross-Priming / immunology
Dose-Response Relationship, Immunologic
Ethnicity
Female
Humans
Immunity
Immunoglobulin G / immunology
Linear Models
Male
Middle Aged
Reference Standards
SARS-CoV-2 / immunology
T-Lymphocytes / immunology
Treatment Outcome
Vaccines, Synthetic / immunology*
Young Adult
mRNA Vaccines

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Vaccines, Synthetic
BNT162 Vaccine

Abstract

Publication types

MeSH terms

Substances

Grants and funding