Correlation between post-vaccination titres of combined IgG, IgA, and IgM anti-Spike antibodies and protection against breakthrough SARS-CoV-2 infection: a population-based longitudinal study (COVIDENCE UK)

Vivaldi, Giulia; Jolliffe, David A.; Faustini, Sian; Holt, Hayley; Perdek, Natalia; Talaei, Mohammad; Tydeman, Florence; Chambers, Emma S.; Cai, Weigang; Li, Wenhao; Gibbons, Joseph M.; Pade, Corinna; Shaheen, Seif O.; Richter, Alex G; Martineau, Adrian R.

doi:10.1101/2022.02.11.22270667

Cited by 7 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We utilised a CE-marked assay with high sensitivity and specificity that targets three different types of antibody, 21 and that we have validated as a correlate of protection against breakthrough disease. 22,23 Its large size affords power to detect determinants of having undetectable anti-spike antibodies after SARS-CoV-2 vaccination – a relatively rare, but potentially clinically important outcome. The population-based nature of this study, and the fact that we investigated effects of two major vaccines utilising differing technology (one live vector, one mRNA) enhances the generalisability of our findings.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK)

Jolliffe

Faustini

Holt

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

SummaryBackgroundAntibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood.MethodsWe tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021.FindingsSerology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs.InterpretationWe identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2.Study registrationhttps://clinicaltrials.gov/ct2/show/NCT04330599FundingBarts Charity, Fischer Family Trust, The Exilarch’s Foundation, DSM Nutritional Products, Health Data Research UKResearch in contextEvidence before this studyWe searched PubMed, medRxiv, and Google Scholar for papers published from January 1, 2020, to February 1, 2022, using the search terms (antibody OR humoral OR serologic* OR immunogenic*) AND (SARS-CoV-2 vaccine OR ChAdOx1 or BNT162b2 coronavirus), with no language restrictions. Population-based studies investigating multiple potential determinants of vaccine immunogenicity in people with known pre-vaccination SARS-CoV-2 serostatus are lacking.Added value of this studyThis large population-based study, conducted in a population with known pre-vaccination SARS-CoV-2 serostatus, examines a comprehensive range of potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of antibody responses to administration of two major SARS-CoV-2 vaccines (i.e., ChAdOx1 or BNT162b2), many of which have not previously been investigated. It is also the first population-based study to characterise antibody responses to booster doses of SARS-CoV-2 vaccines in adults who were seronegative after their primary course of vaccination.Implications of all the available evidenceIncreased risk of seronegativity following two doses of SARS-CoV-2 vaccines was associated with administration of ChAdOx1 vs BNT162b2, shorter interval between first and second vaccine doses, poorer self-assessed general health, immunocompromise and SARS-CoV-2 seronegativity pre-vaccination. Regular intake of vitamin D supplements was associated with reduced risk of post-vaccination seronegativity. Randomised controlled trials are now needed to test for causality. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in the majority of people who failed to mount antibody responses following a primary course of vaccination, the few exceptions being a subset of those with primary immunodeficiency or systemic immunosuppressant drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

“…We utilised an assay with proven sensitivity for detection of combined IgG, IgA and IgM antibodies to the SARS-CoV-2 spike antigen 21 that has been validated as a correlate of protection against breakthrough COVID-19 in two populations. 22,23…”

Section: Introductionmentioning

confidence: 99%

Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK)

Jolliffe

Faustini

Holt

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…• Analyses of post-vaccination serology data showed that higher post-vaccination titres of anti-S antibodies associated with self-report of reactive symptoms following SARS-CoV-2 vaccination 11 and were a correlate of protection against breakthrough COVID-19. 12 We also identified several factors associating with lower anti-S antibody titres following a primary course of vaccination against SARS-CoV-2, including vaccination with ChAdOx1 nCoV-19 (Oxford AstraZeneca, ChAdOx1) vs. BNT162b2 (Pfizer), a shorter interval between vaccine doses, poor vs. excellent self-rated general health, immunodeficiency and use of immunosuppressant medications. Among a subset of 247 participants who were seronegative following their primary course of vaccination, administration of a single booster dose of mRNA vaccine was effective in achieving seroconversion in all but eight individuals, all of whom had a known immunodeficiency or were taking immunosuppressant medication.…”

Section: Resultsmentioning

confidence: 99%

“…Among a subset of 247 participants who were seronegative following their primary course of vaccination, administration of a single booster dose of mRNA vaccine was effective in achieving seroconversion in all but eight individuals, all of whom had a known immunodeficiency or were taking immunosuppressant medication. 10 • Analyses investigating incidence of SARS-CoV-2 infection in vaccinated participants showed that post-vaccination titres of anti-S antibodies were a correlate of protection against breakthrough COVID-19, 12 and that risk of breakthrough disease was independently associated with younger vs. older age, lower vs. higher educational attainment, administration of ChAdOx1 vs.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK)

Holt

Relton

Talaei

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is estimated to have caused more than 18 million deaths worldwide as of end-May 2022. Methods: COVIDENCE UK is a longitudinal population-based study that investigates risk factors for, and impacts of, COVID-19 in UK residents aged ≥16 years. A unique feature is the capacity to support trial-within-cohort studies to evaluate interventions for prevention of COVID-19 and other acute respiratory illnesses. Participants complete a detailed online baseline questionnaire capturing self-reported information relating to their socio-demographic characteristics, occupation, lifestyle, quality of life, weight, height, longstanding medical conditions, medication use, vaccination status, diet and supplemental micronutrient intake. Follow-up on-line questionnaires capturing incident symptoms of COVID-19 and other acute respiratory infections, incident swab test-confirmed COVID-19, doses of SARS-CoV-2 vaccine received, and quality of life are completed at monthly intervals. Results: The study was launched on 1st May 2020 and closed to recruitment on 6th October 2021. A total of 19,981 participants enrolled and consented to 5-year follow-up with medical record linkage. Their mean age was 59.1 years (range 16.0 to 94.4 years), 70.2% were female, and 93.7% identified their ethnic origin as White. Analyses conducted to date have provided key insights into risk factors for SARS-CoV-2 infection and COVID-19 disease, determinants of SARS-CoV-2 vaccine immunogenicity and efficacy, and impacts of COVID-19 on health economic outcomes. The cohort has also supported conduct of a Phase 3 randomised trial-within-cohort study (CORONAVIT) evaluating implementation of a test-and-treat approach to correcting sub-optimal vitamin D status on incidence and severity of acute respiratory infections, including COVID-19. Conclusions: The COVIDENCE UK dataset represents a valuable resource containing granular information on factors influencing susceptibility to, and impacts of, COVID-19 in UK adults. Researchers wishing to access anonymised participant-level data should contacting the corresponding author for further information.

show abstract

Germline variants of IGHV3-53 / V3-66 are determinants of antibody responses to the BNT162b2 mRNA COVID-19 vaccine

Mashimo

Yamazaki²,

Kageyama³

et al. 2022

Journal of Infection

View full text Add to dashboard Cite

Correlation between post-vaccination titres of combined IgG, IgA, and IgM anti-Spike antibodies and protection against breakthrough SARS-CoV-2 infection: a population-based longitudinal study (COVIDENCE UK)

Cited by 7 publications

References 15 publications

Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK)

Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK)

Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK)

Germline variants of IGHV3-53 / V3-66 are determinants of antibody responses to the BNT162b2 mRNA COVID-19 vaccine

Contact Info

Product

Resources

About