TY - JOUR
T1 - Antibody levels following vaccination against SARSCoV-2
T2 - associations with post-vaccination infection and risk factors in two UK longitudinal studies
AU - Cheetham, Nathan J.
AU - Kibble, Milla
AU - Wong, Andrew
AU - Silverwood, Richard J.
AU - Knuppel, Anika
AU - Williams, Dylan M.
AU - Hamilton, Olivia K.L.
AU - Lee, Paul H.
AU - Staatz, Charis Bridger
AU - Di Gessa, Giorgio
AU - Zhu, Jingmin
AU - Katikireddi, Srinivasa Vittal
AU - Ploubidis, George B.
AU - Thompson, Ellen J.
AU - Bowyer, Ruth C.E.
AU - Zhang, Xinyuan
AU - Abbasian, Golboo
AU - Garcia, Maria Paz
AU - Hart, Deborah
AU - Seow, Jeffrey
AU - Graham, Carl
AU - Kouphou, Neophytos
AU - Acors, Sam
AU - Malim, Michael H.
AU - Mitchell, Ruth E.
AU - Northstone, Kate
AU - Major-Smith, Daniel
AU - Matthews, Sarah
AU - Breeze, Thomas
AU - Crawford, Michael
AU - Molloy, Lynn
AU - Kwong, Alex S.F.
AU - Doores, Katie J.
AU - Chaturvedi, Nishi
AU - Duncan, Emma L.
AU - Timpson, Nicholas J.
AU - Steves, Claire J.
N1 - Funding Information:
is funded by COVID-19 Longitudinal Health and Wellbeing – National Core Study (LHW-NCS)
Funding Information:
Antibody testing was funded by UK Health Security Agency. The National Core Studies program
Funding Information:
NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215-2001), the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A29019). MK is supported by the Medical Research Council (MR/W021315/1). AK is supported by Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services (CONVALESCENCE) funded by NIHR (COV-LT-0009). SVK acknowledges funding from an NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). OKLH is supported by the Medical Research Council (MC_UU_12017/11 and MC_UU_00022/3) and the Scottish Government Chief Scientist Office (SPHSU17).This publication is the work of the authors and NJC, NJT and CJS serve as guarantors for the contents of this paper.
Funding Information:
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.
Publisher Copyright:
© 2023, eLife Sciences Publications Ltd. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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) 3 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.
AB - 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) 3 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.
KW - antibodies
KW - breakthrough infection
KW - COVID-19
KW - Key terms: ALSPAC
KW - SARS-CoV-2
KW - serology
KW - TwinsUK
KW - vaccination
UR - http://www.scopus.com/inward/record.url?scp=85147156282&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/eLife.80428
DO - https://doi.org/10.7554/eLife.80428
M3 - Article
AN - SCOPUS:85147156282
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
M1 - e80428
ER -