Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study

  1. Giulia Vivaldi
  2. David A Jolliffe
  3. Sian Faustini
  4. Adrian M Shields
  5. Hayley Holt
  6. Natalia Perdek
  7. Mohammad Talaei
  8. Florence Tydeman
  9. Emma S Chambers
  10. Weigang Cai
  11. Wenhao Li
  12. Joseph M Gibbons
  13. Corinna Pade
  14. Áine McKnight
  15. Seif O Shaheen
  16. Alex G Richter
  17. Adrian R Martineau

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Abstract

In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 [95% confidence interval, .72–.86]; P < .001) and S peptide–stimulated interferon-γ concentrations (rs = 0.31 [.13–.47]; P < .001).

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  1. Version published to 10.1093/infdis/jiac321
  2. ScreenIT

    SciScore for 10.1101/2022.02.11.22270667: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Semi-quantitative determination of antibody titres in dried blood spot eluates was done using a commercially available ELISA that detects anti-Spike IgG/A/M with 98.3% specificity and 98.6% sensitivity (product code MK654; The Binding Site, Birmingham, UK).
    anti-Spike IgG/A/M
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were done using Stata/MP (version 17.0) and GraphPad Prism (version 9.1.2).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    A limitation of our study is that our findings are limited to recipients of ChAdOx1 and BNT162b2 vaccines, although these are two of the most widely administered vaccines and operate via different mechanisms. We also lacked statistical power in our analysis of breakthrough infection following vaccination with BNT162b2, because of fewer participants and lower rates of infection. Finally, our results are not generalisable to children or populations of non-White ethnicity. In conclusion, our combined measure of anti-Spike IgG/A/M was only modestly predictive of breakthrough infection in vaccinated individuals, and performance was significantly improved by incorporating factors reflecting post-vaccination SARS-CoV-2 exposure. Combined with the poor correlation observed between anti-Spike IgG/A/M and S peptide-stimulated IFN-γ, these findings suggest that the relatively limited predictive value of anti-Spike IgG/A/M titres for protection may reflect their inability to reflect protective vaccine-induced cellular responses.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04330599Active, not recruitingLongitudinal Population-based Observational Study of COVID-1…

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2022.02.11.22270667 on medRxiv