Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies

Abstract

Background: SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts.

Methods: Samples were collected from 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N = 4,256; ALSPAC, N = 4,622), and in TwinsUK only in November 2021-January 2022 (N = 3,575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables.

Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (2- to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations.

Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies.

Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC (MC_PC_20030 & MC_PC_20059). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant COV-LT-0009). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC.

Data availability

Data from all analyses presented in figures and tables herein are tabulated and available as a supplementary spreadsheet file. Original antibody test data are available within the UK Longitudinal Linkage Collaboration upon application (see https://ukllc.ac.uk/apply/). UK LLC houses COVID-19 related datasets from over 20 UK longitudinal population studies (see https://ukllc.ac.uk/datasets/). Original TwinsUK data are available to researchers on application. Access to original TwinsUK data is managed by the TwinsUK Resource Executive Committee (see https://twinsuk.ac.uk/resources-for-researchers/access-our-data/) and access to original ALSPAC data via an online proposal system (see http://www.bristol.ac.uk/media-library/sites/alspac/documents/researchers/data-access/ALSPAC_Access_Policy.pdf). This is to ensure privacy and protect against misuse. ALSPAC study data were collected and managed using REDCap electronic data capture tools hosted at the University of Bristol. REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies (doi:10.1016/J.JBI.2008.08.010). The study website contains details of all the data that is available through a fully searchable data dictionary and variable search tool on the study website (http://www.bristol.ac.uk/alspac/researchers/our-data/). Analysis code will be made openly available via GitHub at: https://github.com/nathan-cheetham.

Article and author information

Author details

  1. Nathan J Cheetham

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    For correspondence
    nathan.cheetham@kcl.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2259-1556
  2. Milla Kibble

    Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    Milla Kibble, received payment for attending the Health and Safety Executive (HSE) symposium. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1130-4010
  3. Andrew Wong

    MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Richard J Silverwood

    Centre for Longitudinal Studies, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Anika Knuppel

    MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  6. Dylan M Williams

    MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Olivia KL Hamilton

    MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5874-0058
  8. Paul H Lee

    Department of Health Sciences, University of Leicester, Leicester, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5729-6450
  9. Charis Bridger Staatz

    Centre for Longitudinal Studies, University College London, London, United Kingdom
    Competing interests
    Charis Bridger Staatz, received an ESRC and NIHR funded Grant, and MRC Funded Studentship. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2872-6968
  10. Giorgio Di Gessa

    Department of Epidemiology and Public Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6154-1845
  11. Jingmin Zhu

    Department of Epidemiology and Public Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8325-7589
  12. Srinivasa Vittal Katikireddi

    MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    Srinivasa Vittal Katikireddi, participates on the Scottish Government Expert Reference Group on Ethnicity and COVID-19, and UK Scientific Advisory Group on Emergencies (SAGE) subgroup on Ethnicity. The author has no other competing interests to declare..
  13. George B Ploubidis

    Centre for Longitudinal Studies, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  14. Ellen J Thompson

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  15. Ruth CE Bowyer

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  16. Xinyuan Zhang

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  17. Golboo Abbasian

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  18. Maria Paz Garcia

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    Maria Paz Garcia, is a member of the King's College London Health Faculties Research Ethics Subcommittee (Purple), and a Chair of the TwinsUK Volunteer Advisory Panel. The author has no other competing interests to declare..
  19. Deborah Hart

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  20. Jeffrey Seow

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  21. Carl Graham

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  22. Neophytos Kouphou

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  23. Sam Acors

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6428-7707
  24. Michael H Malim

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7699-2064
  25. Ruth E Mitchell

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  26. Kate Northstone

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  27. Daniel Major-Smith

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6467-2023
  28. Sarah Matthews

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  29. Thomas Breeze

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  30. Michael Crawford

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  31. Lynn Molloy

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  32. Alex SF Kwong

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    Competing interests
    No competing interests declared.
  33. Katie Doores

    Department of Infectious Diseases, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  34. Nishi chaturvedi

    MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom
    Competing interests
    Nishi chaturvedi, received payment for clinical trials of a diabetes drug from AstraZeneca. Nishi Chaturvedi is Chair of British Heart Foundation Fellowships Committee, a member of Diabetes UK research committee and a member of NWO Gravitational Awards Committee. The author has no other competing interests to declare..
  35. Emma L Duncan

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8143-4403
  36. Nicholas J Timpson

    Population Health Sciences, University of Bristol, Bristol, United Kingdom
    For correspondence
    N.J.Timpson@bristol.ac.uk
    Competing interests
    No competing interests declared.
  37. Claire J Steves

    Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
    For correspondence
    claire.j.steves@kcl.ac.uk
    Competing interests
    Claire J Steves, received payment for consultancy work for Zoe Ltd. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4910-0489

Funding

NIHR (COV-LT-0009)

  • Nathan J Cheetham
  • Milla Kibble
  • Andrew Wong
  • Richard J Silverwood
  • Anika Knuppel
  • Dylan M Williams
  • Olivia KL Hamilton
  • Srinivasa Vittal Katikireddi
  • George B Ploubidis
  • Ellen J Thompson
  • Ruth CE Bowyer
  • Maria Paz Garcia
  • Nishi chaturvedi
  • Nicholas J Timpson
  • Claire J Steves

NIHR Bristol Biomedical Research Centre (BRC-1215-2001)

  • Nicholas J Timpson

MRC Integrative Epidemiology Unit (MC_UU_00011/1)

  • Nicholas J Timpson

Medical Research Council (MR/W021315/1)

  • Milla Kibble

NRS (SCAF/15/02)

  • Srinivasa Vittal Katikireddi

Medical Research Council (MC_UU_00022/2)

  • Srinivasa Vittal Katikireddi

Scottish Government Chief Scientist Office (SPHSU17)

  • Olivia KL Hamilton
  • Srinivasa Vittal Katikireddi

Medical Research Council (MC_UU_12017/11)

  • Olivia KL Hamilton

Medical Research Council (MC_UU_00022/3)

  • Olivia KL Hamilton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The ethics statements for each of the longitudinal studies involved in this study are outlined below. TwinsUK: All waves of TwinsUK have received ethical approval associated with TwinsUK Biobank (19/NW/0187), TwinsUK (EC04/015) or Healthy Ageing Twin Study (H.A.T.S) (07/H0802/84) studies from HRA/NHS Research Ethics Committees. The TwinsUK Resource Executive Committee (TREC) oversees management, data sharing and collaborations involving the TwinsUK registry (for further details see https://twinsuk.ac.uk/resources-forresearchers/access-our-data/), in consultation with the TwinsUK Volunteer Advisory Panel (VAP) where needed. ALSPAC: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). USoc: The University of Essex Ethics Committee has approved all data collection for the Understanding Society main study and COVID-19 web and telephone surveys (ETH1920-1271). The March 2021 web survey was reviewed and ethics approval granted by the NHS Health Research Authority, London - City & East Research Ethics Committee (reference 21/HRA/0644). No additional ethical approval was necessary for this secondary data analysis. 1958 NCDS, 1970 BCS70, Next Steps, MCS: The most recent sweeps of 1958 NCDS, 1970 BCS, Next Steps and MCS have all been granted ethical approval by the National Health Service (NHS) Research Ethics Committee and all participants have given informed consent. ELSA: Waves 1-9 of ELSA were approved by the London Multicentre Research Ethics Committee (approval number MREC/01/2/91),and the COVID-19 sub-study was approved by the University College London Research Ethics Committee (0017/003). All participants provided informed consent. 1946 NSHD: Ethical approval for the study was obtained from the NHS Research Ethics Committee (19/LO/1774). All participants provided informed consent. SABRE: Ethical approval for the study was obtained from the NHS Research Ethics Committee (19/LO/1774). All participants provided informed consent. EXCEED: The original EXCEED study was approved by the Leicester Central Research Ethics Committee (Ref: 13/EM/0226). Substantial amendments have been approved by the same Research Ethics Committee for the collection of new data relating to the COVID-19 pandemic, including the COVID-19 questionnaires and antibody testing.

Reviewing Editor

  1. Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States

Publication history

  1. Received: May 20, 2022
  2. Accepted: December 22, 2022
  3. Accepted Manuscript published: January 24, 2023 (version 1)

Copyright

© 2023, Cheetham et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nathan J Cheetham
  2. Milla Kibble
  3. Andrew Wong
  4. Richard J Silverwood
  5. Anika Knuppel
  6. Dylan M Williams
  7. Olivia KL Hamilton
  8. Paul H Lee
  9. Charis Bridger Staatz
  10. Giorgio Di Gessa
  11. Jingmin Zhu
  12. Srinivasa Vittal Katikireddi
  13. George B Ploubidis
  14. Ellen J Thompson
  15. Ruth CE Bowyer
  16. Xinyuan Zhang
  17. Golboo Abbasian
  18. Maria Paz Garcia
  19. Deborah Hart
  20. Jeffrey Seow
  21. Carl Graham
  22. Neophytos Kouphou
  23. Sam Acors
  24. Michael H Malim
  25. Ruth E Mitchell
  26. Kate Northstone
  27. Daniel Major-Smith
  28. Sarah Matthews
  29. Thomas Breeze
  30. Michael Crawford
  31. Lynn Molloy
  32. Alex SF Kwong
  33. Katie Doores
  34. Nishi chaturvedi
  35. Emma L Duncan
  36. Nicholas J Timpson
  37. Claire J Steves
(2023)
Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies
eLife 12:e80428.
https://doi.org/10.7554/eLife.80428

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    Methods: We included all women aged 23-64 years old invited to participate in cervical cancer screening from 2015-2021 as registered in the Cervical Cancer Screening Database combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of cervical cancer screening participation within 90, 180 and 365 days since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.

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    Funding: The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.

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