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

Nathan J. Cheetham; Milla Kibble; Andrew Wong; Richard J. Silverwood; Anika Knuppel; Dylan M. Williams; Olivia K.L. Hamilton; Paul H. Lee; Charis Bridger Staatz; Giorgio Di Gessa; Jingmin Zhu; Srinivasa Vittal Katikireddi; George B. Ploubidis; Ellen J. Thompson; Ruth C.E. Bowyer; Xinyuan Zhang; Golboo Abbasian; Maria Paz Garcia; Deborah Hart; Jeffrey Seow; Carl Graham; Neophytos Kouphou; Sam Acors; Michael H. Malim; Ruth E. Mitchell; Kate Northstone; Daniel Major-Smith; Sarah Matthews; Thomas Breeze; Michael Crawford; Lynn Molloy; Alex S.F. Kwong; Katie J. Doores; Nishi Chaturvedi; Emma L. Duncan; Nicholas J. Timpson; Claire J. Steves

doi:10.7554/eLife.80428

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

Nathan J. Cheetham^*, Milla Kibble, Andrew Wong, Richard J. Silverwood, Anika Knuppel, Dylan M. Williams, Olivia K.L. Hamilton, Paul H. Lee, Charis Bridger Staatz, Giorgio Di Gessa, Jingmin Zhu, Srinivasa Vittal Katikireddi, George B. Ploubidis, Ellen J. Thompson, Ruth C.E. Bowyer, Xinyuan Zhang, Golboo Abbasian, Maria Paz Garcia, Deborah Hart, Jeffrey SeowCarl Graham, Neophytos Kouphou, Sam Acors, Michael H. Malim, Ruth E. Mitchell, Kate Northstone, Daniel Major-Smith, Sarah Matthews, Thomas Breeze, Michael Crawford, Lynn Molloy, Alex S.F. Kwong, Katie J. Doores, Nishi Chaturvedi, Emma L. Duncan, Nicholas J. Timpson^*, Claire J. Steves^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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) 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.

Original language	English
Article number	e80428
Journal	eLife
Volume	12
Early online date	24 Jan 2023
DOIs	https://doi.org/10.7554/eLife.80428 https://doi.org/10.7554/eLife.80428
Publication status	Published - 2023

Keywords

antibodies
breakthrough infection
COVID-19
Key terms: ALSPAC
SARS-CoV-2
serology
TwinsUK
vaccination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cheetham, N. J., Kibble, M., Wong, A., Silverwood, R. J., Knuppel, A., Williams, D. M., Hamilton, O. K. L., Lee, P. H., Staatz, C. B., Di Gessa, G., Zhu, J., Katikireddi, S. V., Ploubidis, G. B., Thompson, E. J., Bowyer, R. C. E., Zhang, X., Abbasian, G., Garcia, M. P., Hart, D., ... Steves, C. J. (2023). Antibody levels following vaccination against SARSCoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies. eLife, 12, Article e80428. https://doi.org/10.7554/eLife.80428, https://doi.org/10.7554/eLife.80428

@article{478f96c5ec174b178b74132a1852a74d,

title = "Antibody levels following vaccination against SARSCoV-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) 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{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}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.",

keywords = "antibodies, breakthrough infection, COVID-19, Key terms: ALSPAC, SARS-CoV-2, serology, TwinsUK, vaccination",

author = "Cheetham, {Nathan J.} and Milla Kibble and Andrew Wong and Silverwood, {Richard J.} and Anika Knuppel and Williams, {Dylan M.} and Hamilton, {Olivia K.L.} and Lee, {Paul H.} and Staatz, {Charis Bridger} and {Di Gessa}, Giorgio and Jingmin Zhu and Katikireddi, {Srinivasa Vittal} and Ploubidis, {George B.} and Thompson, {Ellen J.} and Bowyer, {Ruth C.E.} and Xinyuan Zhang and Golboo Abbasian and Garcia, {Maria Paz} and Deborah Hart and Jeffrey Seow and Carl Graham and Neophytos Kouphou and Sam Acors and Malim, {Michael H.} and Mitchell, {Ruth E.} and Kate Northstone and Daniel Major-Smith and Sarah Matthews and Thomas Breeze and Michael Crawford and Lynn Molloy and Kwong, {Alex S.F.} and Doores, {Katie J.} and Nishi Chaturvedi and Duncan, {Emma L.} and Timpson, {Nicholas J.} and Steves, {Claire J.}",

note = "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{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}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: {\textcopyright} 2023, eLife Sciences Publications Ltd. All rights reserved.",

year = "2023",

doi = "10.7554/eLife.80428",

language = "English",

volume = "12",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications, Ltd",

}

Cheetham, NJ, Kibble, M, Wong, A, Silverwood, RJ, Knuppel, A, Williams, DM, Hamilton, OKL, Lee, PH, Staatz, CB, Di Gessa, G, Zhu, J, Katikireddi, SV, Ploubidis, GB, Thompson, EJ , Bowyer, RCE , Zhang, X, Abbasian, G, Garcia, MP, Hart, D, Seow, J, Graham, C, Kouphou, N , Acors, S , Malim, MH, Mitchell, RE, Northstone, K, Major-Smith, D, Matthews, S, Breeze, T, Crawford, M, Molloy, L, Kwong, ASF, Doores, KJ, Chaturvedi, N, Duncan, EL, Timpson, NJ & Steves, CJ 2023, 'Antibody levels following vaccination against SARSCoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies', eLife, vol. 12, e80428. https://doi.org/10.7554/eLife.80428, https://doi.org/10.7554/eLife.80428

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 - 10.7554/eLife.80428

DO - 10.7554/eLife.80428

M3 - Article

AN - SCOPUS:85147156282

SN - 2050-084X

VL - 12

JO - eLife

JF - eLife

M1 - e80428

ER -

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

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Keywords

UN SDGs

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