Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Shona C Moore; Barbara Kronsteiner; Stephanie Longet; Sandra Adele; Alexandra S Deeks; Chang Liu; Wanwisa Dejnirattisai; Laura Silva Reyes; Naomi Meardon; Sian Faustini; Saly Al-Taei; Tom Tipton; Luisa M Hering; Adrienn Angyal; Rebecca Brown; Alexander R Nicols; Susan L Dobson; Piyada Supasa; Aekkachai Tuekprakhon; Andrew Cross; Jessica K Tyerman; Hailey Hornsby; Irina Grouneva; Megan Plowright; Peijun Zhang; Thomas A H Newman; Jeremy M Nell; Priyanka Abraham; Mohammad Ali; Tom Malone; Isabel Neale; Eloise Phillips; Joseph D Wilson; Sam M Murray; Martha Zewdie; Adrian Shields; Emily C Horner; Lucy H Booth; Lizzie Stafford; Sagida Bibi; Daniel G Wootton; Alexander J Mentzer; Christopher P Conlon; Katie Jeffery; Philippa C Matthews; Andrew J Pollard; Anthony Brown; Sarah L Rowland-Jones; Juthathip Mongkolsapaya; Rebecca P Payne; Christina Dold; Teresa Lambe; James E D Thaventhiran; Gavin Screaton; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christopher J A Duncan; Alex Richter; Miles Carroll; Thushan I de Silva; Paul Klenerman; Susanna Dunachie; Lance Turtle; PITCH Consortium

doi:10.1016/j.medj.2023.02.004

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Med. 2023 Mar 10;4(3):191-215.e9. doi: 10.1016/j.medj.2023.02.004. Epub 2023 Feb 16.

Authors

Shona C Moore¹, Barbara Kronsteiner², Stephanie Longet³, Sandra Adele², Alexandra S Deeks⁴, Chang Liu⁵, Wanwisa Dejnirattisai⁶, Laura Silva Reyes⁷, Naomi Meardon⁸, Sian Faustini⁹, Saly Al-Taei⁹, Tom Tipton³, Luisa M Hering¹, Adrienn Angyal¹⁰, Rebecca Brown¹⁰, Alexander R Nicols¹¹, Susan L Dobson¹, Piyada Supasa¹², Aekkachai Tuekprakhon¹², Andrew Cross¹³, Jessica K Tyerman¹¹, Hailey Hornsby¹⁰, Irina Grouneva¹⁰, Megan Plowright¹⁴, Peijun Zhang¹⁰, Thomas A H Newman¹⁴, Jeremy M Nell¹⁵, Priyanka Abraham², Mohammad Ali², Tom Malone¹⁶, Isabel Neale², Eloise Phillips¹⁶, Joseph D Wilson¹⁷, Sam M Murray¹⁶, Martha Zewdie¹⁶, Adrian Shields¹⁸, Emily C Horner¹⁹, Lucy H Booth¹⁹, Lizzie Stafford¹², Sagida Bibi⁷, Daniel G Wootton²⁰, Alexander J Mentzer²¹, Christopher P Conlon²², Katie Jeffery²³, Philippa C Matthews²⁴, Andrew J Pollard²⁵, Anthony Brown¹⁶, Sarah L Rowland-Jones¹⁴, Juthathip Mongkolsapaya⁵, Rebecca P Payne¹¹, Christina Dold²⁶, Teresa Lambe²⁷, James E D Thaventhiran¹⁹, Gavin Screaton⁵, Eleanor Barnes²⁸, Susan Hopkins²⁹, Victoria Hall³⁰, Christopher J A Duncan³¹, Alex Richter¹⁸, Miles Carroll³, Thushan I de Silva¹⁴, Paul Klenerman³², Susanna Dunachie³³, Lance Turtle³⁴; PITCH Consortium

Affiliations

¹ NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
² Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
³ Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, 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.
⁵ 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.
⁶ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Division of Emerging Infectious Disease, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁸ Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
⁹ Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK.
¹⁰ Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
¹¹ Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle, UK.
¹² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹³ Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
¹⁴ Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
¹⁵ Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
¹⁶ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, 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 Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK; University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹⁹ MRC Toxicology Unit, University of Cambridge, Cambridge, UK.
²⁰ 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.
²¹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
²² Oxford Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
²³ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²⁴ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, 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.
²⁵ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
²⁶ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
²⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
²⁸ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
²⁹ UK Health Security Agency, 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.
³⁰ UK Health Security Agency, London, UK; NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK.
³¹ 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 upon Tyne, UK.
³² Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK. Electronic address: paul.klenerman@ndm.ox.ac.uk.
³³ Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, 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; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
³⁴ 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. Electronic address: lance.turtle@liverpool.ac.uk.

Abstract

Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination.

Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination.

Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose.

Conclusions: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease.

Funding: Department for Health and Social Care, Medical Research Council.

Keywords: COVID vaccine; COVID-19; SARS-CoV-2; T cells; Translation to population health; antibody; immunity.

Publication types

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

MeSH terms

Antibodies, Neutralizing
BNT162 Vaccine
COVID-19 Vaccines
COVID-19*
ChAdOx1 nCoV-19
Health Personnel
Humans
Immunity, Humoral
Prospective Studies
SARS-CoV-2
Vaccines*

Substances

COVID-19 Vaccines
BNT162 Vaccine
ChAdOx1 nCoV-19
Vaccines
Antibodies, Neutralizing

Abstract

Publication types

MeSH terms

Substances

Grants and funding