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.
| Original language | English |
|---|---|
| Pages (from-to) | 191-215.e9 |
| Journal | Med |
| Volume | 4 |
| Issue number | 3 |
| Early online date | 16 Feb 2023 |
| DOIs | |
| Publication status | Published - 10 Mar 2023 |
Bibliographical note
Funding Information: We are grateful to all our healthcare worker colleagues who participated in the study. For the Birmingham participants, the study was carried out at the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. Laboratory studies were undertaken by the Clinical Immunology Service, University of Birmingham. This work was funded by the UK Department of Health and Social Care as part of the PITCH Consortium, UKRI as part of Investigation of Proven Vaccine Breakthrough by SARS-CoV-2 Variants in Established UK Healthcare Worker cohorts: SIREN consortium & PITCH Plus Pathway, MR/W02067X/1, with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation, and the National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, grant reference number COV19-RECPLAS). E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA. S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). T.d.S. is funded by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). R.P.P. is funded by a Career Re-entry Fellowship (204721/Z/16/Z). C.J.A.D. is funded by a Wellcome Clinical Research Career Development Fellowship (211153/Z/18/Z). J.M. and G.S. are funded by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number 2018-I2M-2-002), Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. The Wellcome Center for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). P.C.M. is funded by Wellcome (110,110z/15/Z), the Francis Crick Institute, and the University College London Hospital NIHR Biomedical Research Center. J.E.D.T. is supported by the Medical Research Council (MR/W020564/1) and (MC_UU_0025/12). L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z), the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (EZI) (NIHR200907), and the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity. The HPRU-EZI at the University of Liverpool is in partnership with UK Health Security Agency (UKHSA), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. D.G.W. is supported by an NIHR Advanced Fellowship in Liverpool. M.C. S.L. L.T. and T.T. are supported by the US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085. The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-ObS) was supported by the British Heart Foundation (PG/11/116/29,288). The STH-ObS Chief Investigator Allan Laurie is supported by a British Heart Foundation Senior Basic Science Research fellowship (FS/18/52/33808). We gratefully acknowledge financial support from the UK Department of Health and Social Care via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, Public Health England, or the US Food and Drug Administration.S.J.D. is a Scientific Advisor to the Scottish Parliament on COVID-19, for which she receives a fee. A.J.P. is Chair of UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) but does not participate in policy decisions on COVID-19 vaccines. He was previously a member of the WHO's SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. A.J.P. is chief investigator on clinical trials of Oxford University's COVID-19 vaccine funded by NIHR. Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca. G.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology.
Open Access: Free to read, but no Open Access licence.
Publisher Copyright: © 2023 Published by Elsevier Inc.
Citation: 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, Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens, Med, Volume 4, Issue 3, 2023, Pages 191-215.e9, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2023.02.004.
(https://www.sciencedirect.com/science/article/pii/S2666634023000648)
DOI: https://doi.org/10.1016/j.medj.2023.02.004.
Keywords
- COVID vaccine
- COVID-19
- SARS-CoV-2
- T cells
- Translation to population health
- antibody
- immunity
