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

10.1101/2022.06.06.22275865

MedRxiv

7th June 2022

Contributing to research themes:

This research has not been peer-reviewed.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:

Affiliations

NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
Oxford Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, UK
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK
Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Division of Emerging Infectious Disease, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, UK
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, UK
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, UK
Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
Oxford University Medical School, Medical Sciences Division, University of Oxford, Oxford, UK
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
MRC Toxicology Unit, University of Cambridge, Cambridge, UK
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
Radcliffe Department of Medicine, University of Oxford, UK
The Francis Crick Institute, London, UK
Division of Infection and Immunity, University College London, London, UK
Department of Infectious Diseases, University College London Hospital NHS Foundation Trust, London, UK
NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK
Translational Gastroenterology Unit, University of Oxford, UK
UK Health Security Agency, London, UK
Faculty of Medicine, Department of Infectious Disease, Imperial College London, UK
NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, UK
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand

Authors

Shona C. Moore¹*, Barbara Kronsteiner^2,3*, Stephanie Longet^4,5*, Sandra Adele*^2,3, Alexandra S. Deeks^2,6, Chang Liu⁵, Wanwisa Dejnirattisai^5,7, Laura Silva Reyes⁸, Naomi Meardon⁹, Sian Faustini¹⁰, Saly Al-Taei¹⁰, Tom Tipton^4,5, 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 Plowright^9,11, Peijun Zhang¹¹, Thomas A.H. Newman^9,11, Jeremy M. Nell¹⁴, Priyanka Abraham^2,3, Mohammad Ali^2,3, Tom Malone², Isabel Neale^2,3, Eloise Phillips², Joseph D. Wilson^{2, 6,15}, Adrian Shields^10,16, Emily C. Horner¹⁷, Lucy H. Booth¹⁷, Lizzie Stafford⁵, Sagida Bibi⁸, Daniel G. Wootton^1,13,18, Alexander J. Mentzer^5,6, Christopher P. Conlon^3,5, Katie Jeffery^6,19, Philippa C. Matthews^2,20,21,22, Andrew J. Pollard^5,8,23, Anthony Brown², Sarah L. Rowland-Jones^9,11, Juthathip Mongkolsapaya^5,24, Rebecca P. Payne¹², Christina Dold^8,23, Teresa Lambe^8,24, James E.D. Thaventhiran¹⁷, Gavin Screaton^5,24, Eleanor Barnes^2,6,23,25, Susan Hopkins^26,27,28, Victoria Hall^26,28, Christopher JA Duncan^12,14†, Alex Richter^10,16†, Miles Carroll^4,5†, , Thushan I. de Silva^9,11†, Paul Klenerman^2,6,23,25†, Susanna Dunachie^2,3,6,29†, Lance Turtle^1,13,† on behalf of the PITCH Consortium+