Spike-antibody responses to ChAdOx1 and BNT162b2 vaccines by demographic and clinical factors (Virus Watch study)

  1. Madhumita Shrotri
  2. Ellen Fragaszy
  3. Cyril Geismar
  4. Vincent Nguyen
  5. Sarah Beale
  6. Isobel Braithwaite
  7. Thomas E Byrne
  8. Wing Lam Erica Fong
  9. Jana Kovar
  10. Annalan M D Navaratnam
  11. Parth Patel
  12. Anna Aryee
  13. Jamie Lopez Bernal
  14. Anne M Johnson
  15. Alison Rodger
  16. Andrew C Hayward
  17. Robert W Aldridge

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Abstract

Background

Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UK’s extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose.

Methods

Adults aged ≥18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (≥0.8 U/ml), as per Roche’s Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors.

Results

8,837 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 17,160 samples (10,508 following ChAdOx1, 6,547 following BNT162b2). Seropositivity to Spike was 96.79% (95% CI 96.42, 97.12) from 28 days following a single dose, reaching 99.34% (98.91, 99.60) from 14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence for lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men compared with women (26.50 vs 44.01 U/ml, p<0.0001), those with any chronic condition (33.8 vs 43.83 U/ml, p<0.0001), diabetes (22.46 vs 36.90 U/ml, p<0.0001), cardiovascular disease (32.9 vs 37.9 U/ml, p=0.0002), obesity (27.2 vs 37.42, p<0.0001), cancer diagnosis (31.39 vs 36.50 U/ml, p=0.0001), particularly those with haematological cancers (7.94 vs 32.50 U/ml, p<0.0001), and for those currently on statin therapy (30.03 vs 39.39, p<0.0001), or on any immunosuppressive therapy (28.7 vs 36.78 U/ml, p<0.0001), particularly those on oral steroids (16.8 vs 36.07, p<0.0001). Following a second dose, high S-antibody titres (≥250U/ml) were observed across all groups.

Interpretation

A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. Observed disparities in antibody levels by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures for partially vaccinated adults, particularly those who are older and more clinically vulnerable; and high antibody levels across all groups following a second dose demonstrate the importance of complete vaccination. However, the relationship between Spike-antibody levels and protection against COVID-19, and thus the clinical significance of observed disparities, is not yet clear.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.12.21257102: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Individuals aged ≥18 years within eligible households were provided with a participant information sheet and gave valid, informed consent through an electronic REDCap form.
    IRB: Ethical approval This study has been approved by the Hampstead NHS Health Research Authority Ethics Committee.
    Sex as a biological variableSex was limited to Male and Female with other categories suppressed due to small numbers.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Analysis was conducted in Stata version 16.0 (StataCorp, TX, USA) and R (version 4.0.3).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and Limitations The strengths of this study include the large community cohort, which spans many ages and ethnic groups, and includes large numbers of individuals with common chronic conditions as well as capturing those with rarer diagnoses. These data constitute some of the earliest real-world evidence on immunogenicity for many clinical groups, and for ChAdOx1 more broadly, and are likely to be generalisable to other high-income settings deploying these vaccines. We employed a highly sensitive, widely used validated commercial assay that gives quantitative readouts on a linear scale, allowing these data to be easily understood, replicated, and informative for clinical practitioners. Limitations include the use of self-reported vaccination status, which may have introduced error into the assignment of vaccination date and type, or the omission of a recent second dose for some individuals; and collection of clinical data at enrolment only, which may have led to misclassification due to more recent diagnoses. Additionally, the cancer categories encompassed both prior and current diagnoses. Due to the available assay platform and dilution capabilities, the dynamic range of the S-antibody assay was limited to 0.4U/ml - 250U/ml, which precluded differentiation of S-antibody levels between groups following the second dose and amongst those with prior infection. Due to small numbers of individuals with HIV, immunosuppressive cancer therapy, and immunosuppression followin...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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