SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 and correlates of protection in the UK general population

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Abstract

We investigated anti-spike IgG antibody responses and correlates of protection following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, while declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses and 5-8 months after two BNT162b2 doses in those without prior infection, and 1-2 years for those unvaccinated after natural infection. A third booster dose may be needed, prioritised to ChAdOx1 recipients and those more clinically vulnerable.

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  1. SciScore for 10.1101/2021.09.13.21263487: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory testing: SARS-CoV-2 antibody levels were measured on venous or capillary blood samples using an ELISA detecting anti-trimeric spike IgG developed by the University of Oxford36,38.
    anti-trimeric spike IgG
    suggested: None
    We used linear generalized additive models (GAMs) to model anti-spike IgG antibody measurements after the first and second dose.
    anti-spike IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    After this, it used a commercialised CE-marked version of the assay, the Thermo Fisher OmniPATH 384 Combi SARS-CoV-2 IgG ELISA (Thermo Fisher Scientific), with the same antigen and colorimetric detection.
    Thermo Fisher OmniPATH
    suggested: None
    Combined nose and throat swabs were tested by PCR assays using the Thermo Fisher TaqPath SARS-CoV-2 assay at high-throughput national ‘Lighthouse’ laboratories in Glasgow and Milton Keynes (up until 8 February 2021).
    Thermo Fisher TaqPath
    suggested: None
    PCR outputs were analysed using UgenTec FastFinder 3.300.5, with an assay-specific algorithm and decision mechanism that allows conversion of amplification assay raw data into test results with minimal manual intervention.
    UgenTec FastFinder
    suggested: None

    Results from OddPub: Thank you for sharing your code.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Study limitations include insufficient data to include two mRNA-1273 Moderna vaccine doses in analyses. We measured anti-spike IgG antibody using a single assay, with the upper limit of quantification approached by a reasonable number of measurements (n=4189, 5.9%) in the few weeks following second BNT162b2 vaccination, potentially leading to under-estimating peak levels and over-estimating half-lives in those with the highest responses, e.g. younger age groups. As antibody responses were calibrated to a monoclonal antibody they can be compared with other studies. Neutralising antibodies and T-cell responses were not measured, but neutralisation titres were strongly correlated with anti-spike IgG titres (Figure S9). We are not currently powered to assess correlates of protection, the relationship between antibody levels and vaccine effectiveness, which requires further investigation. In summary, the second ChAdOx1 or BNT162b2 dose significantly boosts anti-spike IgG levels, and dosing interval has a limited impact on antibody response. This supports reducing the dosing interval to 8 weeks to increase protection against the widespread Delta variant; for BNT162b2, this could probably be reduced further to 3-weeks in those who have not yet received their second dose (predominantly ≤40 years). Older individuals, males, and those with long-term health conditions have substantially faster antibody declines with BNT162b2 but not ChAdOX1. Protection based on current positivity thresh...

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

    IdentifierStatusTitle
    ISRCTN21086382NANA


    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.


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