Evolution of long-term hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study



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This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS–CoV–2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (PITCH, within the larger SIREN study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Here, we report longer follow up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZ1222 (Oxford/AstraZeneca) vaccination and following a subsequent BNT162b2 booster vaccination. We make three important observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and B cell responses were better maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels to post second dose levels and broadened neutralising activity against variants of concern including omicron BA.1, alongside further boosting of T cell responses. Thirdly, prior infection maintained its impact driving larger T cell responses compared to never infected people, including after the third dose. In conclusion, the maintenance of T cell responses in time and against variants of concern may account for continued protection against severe disease.

Author list:


  1. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  2. Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
  3. Oxford Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
  4. Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, UK
  5. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK
  6. Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  7. Division of Emerging Infectious Disease, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  8. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK
  9. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  10. Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, UK
  11. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
  12. Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, UK
  13. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  14. Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
  15. Oxford University Medical School, Medical Sciences Division, University of Oxford, Oxford, UK
  16. University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  17. MRC Toxicology Unit, University of Cambridge, Cambridge, UK
  18. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  19. Radcliffe Department of Medicine, University of Oxford, UK
  20. The Francis Crick Institute, London, UK
  21. Division of Infection and Immunity, University College London, London, UK
  22. Department of Infectious Diseases, University College London Hospital NHS Foundation Trust, London, UK
  23. NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
  24. Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
  25. Translational Gastroenterology Unit, University of Oxford, UK
  26. UK Health Security Agency, London, UK
  27. Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK
  28. NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, UK
  29. Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand


Shona C. Moore1*, Barbara Kronsteiner2,3*, Stephanie Longet4,5*, Sandra Adele*2,3, Alexandra S. Deeks2,6, Chang Liu5, Wanwisa Dejnirattisai5,7, Laura Silva Reyes8, Naomi Meardon9, Sian Faustini10, Saly Al-Taei10, Tom Tipton4,5, Luisa M Hering1, Adrienn Angyal11, Rebecca Brown11, Alexander R Nicols12, Susan L Dobson1, Piyada Supasa5, Aekkachai Tuekprakhon5, Andrew Cross13, Jessica K Tyerman12, Hailey Hornsby11, Irina Grouneva11, Megan Plowright9,11, Peijun Zhang11, Thomas A.H. Newman9,11, Jeremy M. Nell14, Priyanka Abraham2,3, Mohammad Ali2,3, Tom Malone2, Isabel Neale2,3, Eloise Phillips2, Joseph D. Wilson2, 6,15, Adrian Shields10,16, Emily C. Horner17, Lucy H. Booth17, Lizzie Stafford5, Sagida Bibi8, Daniel G. Wootton1,13,18, Alexander J. Mentzer5,6, Christopher P. Conlon3,5, Katie Jeffery6,19, Philippa C. Matthews2,20,21,22, Andrew J. Pollard5,8,23, Anthony Brown2, Sarah L. Rowland-Jones9,11, Juthathip Mongkolsapaya5,24, Rebecca P. Payne12, Christina Dold8,23, Teresa Lambe8,24, James E.D. Thaventhiran17, Gavin Screaton5,24, Eleanor Barnes2,6,23,25, Susan Hopkins26,27,28, Victoria Hall26,28, Christopher JA Duncan12,14†, Alex Richter10,16†, Miles Carroll4,5†, , Thushan I. de Silva9,11†, Paul Klenerman2,6,23,25†, Susanna Dunachie2,3,6,29†, Lance Turtle1,13,† on behalf of the PITCH Consortium+