Dataset Information

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

ABSTRACT:

Background

Severe acute respiratory syndrome coronavirus 2 (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 9361 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=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). 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 threefold greater odds of SARS-CoV-2 infection over the next 6-9 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 (two- to fourfold) 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] and [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.

SUBMITTER: Cheetham NJ

PROVIDER: S-EPMC9940912 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Cheetham Nathan J NJ Kibble Milla M Wong Andrew A Silverwood Richard J RJ Knuppel Anika A Williams Dylan M DM Hamilton Olivia K L OKL Lee Paul H PH Bridger Staatz Charis C Di Gessa Giorgio G Zhu Jingmin J Katikireddi Srinivasa Vittal SV Ploubidis George B GB Thompson Ellen J EJ Bowyer Ruth C E RCE Zhang Xinyuan X Abbasian Golboo G Garcia Maria Paz MP Hart Deborah D Seow Jeffrey J Graham Carl C Kouphou Neophytos N Acors Sam S Malim Michael H MH Mitchell Ruth E RE Northstone Kate K Major-Smith Daniel D Matthews Sarah S Breeze Thomas T Crawford Michael M Molloy Lynn L Kwong Alex S F ASF Doores Katie K Chaturvedi Nishi N Duncan Emma L EL Timpson Nicholas J NJ Steves Claire J CJ

eLife 20230124

<h4>Background</h4>Severe acute respiratory syndrome coronavirus 2 (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 ...[more]

PMID: 36692910

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Project description:BackgroundProspective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.MethodsWe did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.ResultsOf 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.ConclusionsHigher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

Project description:ObjectivesTo examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.DesignCohort study.SettingOxford University Hospitals in the United Kingdom.ParticipantsHealthcare workers who had SARS-CoV-2 serological data available and received two SARS-CoV- 2 vaccinations.Primary outcomePeak SARS-CoV-2 anti-spike IgG responses after the second vaccination and associations with underlying health conditions and the estimated risk of severe COVID-19 using an occupational health risk assessment tool.MethodsWe used univariable and multivariable linear regression models to investigate associations between antibody levels and demographics (age, sex, ethnicity), healthcare role, body mass index, underlying health conditions, vaccination status, prior infection and the Association of Local Authority Medical Advisors COVID-age risk score.Results1635 HCWs had anti-spike IgG measurements 14-84 days after second vaccination and data on any underlying health conditions. Only five HCWs (0.3%), all on immunosuppressive treatment, (including four organ transplant recipients), did not seroconvert after second vaccination. Antibody levels were independently lower with older age, diabetes, immunosuppression, respiratory disorders other than asthma and markedly so in organ transplant recipients. Levels were independently lower in ChAdOx1 versus BNT162b2 recipients and higher following previous infection. HCWs with 'very high' COVID-age risk scores had lower median antibody levels than those with 'low', 'medium' or 'high' risk scores; 4379 AU/mL, compared with 12 337 AU/mL, 9430 AU/mL and 10 524 AU/mL, respectively.ConclusionsTwo vaccine doses are effective in generating antibody responses among HCWs, including those with a high occupational risk. However, HCWs with underlying health conditions, especially diabetes, immunosuppression and organ transplant, had lower antibody levels, and vaccine response monitoring may be needed.

Project description:As of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ∼14-fold, but they also had ∼3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro . There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.

Dataset Information

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

Background

Methods

Results

Conclusions

Funding

Publications

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

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