Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies
- King's College London, United Kingdom
- University of Cambridge, United Kingdom
- University College London, United Kingdom
- University of Glasgow, United Kingdom
- University of Leicester, United Kingdom
- University of Bristol, United Kingdom
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
Olivia KL Hamilton
Charis Bridger Staatz
Daniel Major-Smith
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.
Reviewing Editor
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
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.
Version history
- Received: May 20, 2022
- Preprint posted: May 22, 2022 (view preprint)
- Accepted: December 22, 2022
- Accepted Manuscript published: January 24, 2023 (version 1)
- Version of Record published: February 20, 2023 (version 2)
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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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
Further reading
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- Epidemiology and Global Health
Background:
The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.
Methods:
To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.
Results:
Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.
Conclusions:
Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
Funding:
This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
