Sustained T cell immunity, protection and boosting using extended dosing intervals of BNT162b2 mRNA vaccine


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This research has not been peer-reviewed, and has been posted on pre-print repository medRxiv. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. In a study of 503 healthcare workers, we show that after priming following the first vaccine there is a marked decline in SARS-CoV-2 neutralizing antibody (NAb) levels, but, in contrast, a sustained T cell response to spike protein. This divergent immune profile was accompanied by robust protection from infection over this period from the circulating alpha (B.1.1.7) variant. Importantly, following the second vaccine dose, NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by a clear enrichment of CD4+ T cells expressing IL2. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol and that antiviral T cell responses are a potential mechanism of protection.

Author list:


*Contributed equally to first authorship
†Contributed equally to senior authorship
^Corresponding author
+Additional consortium members in the Appendix

  1. Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University, UK
  2. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK
  3. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  4. Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
  5. Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  6. Nuffield Dept of Clinical Neuroscience, University of Oxford, UK
  7. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK 
  8. Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, UK
  9. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
  10. Public Health England, Colindale, London, UK
  11. Translational Gastroenterology Unit, University of Oxford, UK
  12. Great North Children’s Hospital, Newcastle, UK
  13. University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  14. Oxford University Medical School, Medical Sciences Division, University of Oxford, Oxford, UK
  15. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  16. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK    
  17. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK
  18. NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
  19. Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
  20. Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand
  21. Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK
  22. NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, UK
  23. Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
  24. Oxford Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
  25. Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand


Rebecca P. Payne1*, Stephanie Longet2*, James A. Austin3*, Donal T. Skelly4,5,6*, Wanwisa Dejnirattisai2, Sandra Adele4 , Naomi Meardon7, Sian Faustini8, Saly Al-Taei8, Shona C. Moore3, Tom Tipton2, Luisa M Hering3, Adrienn Angyal9, Rebecca Brown9, Natalie Gillson10, Susan L Dobson3, Ali Amini5,11, Piyada Supasa2, Andrew Cross1, Gurjinder Sandhar9, Jonathan A. Kilby9, Jessica K Tyerman1, Alexander R Nicols1, Thomas Altmann1,12, Hailey Hornsby9, Rachel Whitham7, Eloise Phillips4, Tom Malone4, Alexander Hargreaves2, Adrian Shields13, Ayoub Saei10, Sarah Foulkes10, Lizzie Stafford5, Sile Johnson4,5,14, Daniel G. Wootton3,15,16, Christopher P. Conlon5, Katie Jeffery5, Philippa C. Matthews4,5, John Frater4,5, Alexandra S. Deeks4,5, Christina Dold17,18, Andrew J. Pollard17,18, Anthony Brown4, Sarah L. Rowland-Jones7, Juthathip Mongkolsapaya2,19,20, Eleanor Barnes4,5,11,18, Susan Hopkins10,21,22, Victoria Hall10,22, Christopher JA Duncan1,23†, Alex Richter8,13†, Miles Carroll2†, Gavin Screaton2†, Thushan I. de Silva7,9†, Lance Turtle3,16,†, Paul Klenerman4,5,11,18†^, Susanna Dunachie4,5,24,25† on behalf of the PITCH Consortium+