Large-Scale Study of Antibody Titer Decay following BNT162b2 mRNA Vaccine or SARS-CoV-2 Infection

  1. Ariel Israel
  2. Yotam Shenhar
  3. Ilan Green
  4. Eugene Merzon
  5. Avivit Golan-Cohen
  6. Alejandro A. Schäffer
  7. Eytan Ruppin
  8. Shlomo Vinker
  9. Eli Magen

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Abstract

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, to determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Antibody titers were measured between 31 January 2021, and 31 July 2021 in two mutually exclusive groups: (i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and (ii) SARS-CoV-2 convalescents who had not received the vaccine. A total of 2653 individuals fully vaccinated by two doses of vaccine during the study period and 4361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8–5644.6]) after the second vaccination than in convalescent individuals (median 355.3 AU/mL IQR [141.2–998.7]; p < 0.001). In vaccinated subjects, antibody titers decreased by up to 38% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.

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  1. Version published to 10.3390/vaccines10010064
  2. ScreenIT

    SciScore for 10.1101/2021.08.19.21262111: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was approved by Shamir Medical Center Institutional Review Board (129-2-LEU).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: The Abbot assay has been validated externally(Bryan et al., 2020; Perkmann et al., 2020; Zabelin et al., n.d.) with sensitivity 96.77%, specificity 99% and the caveat that these numbers depend on the boundaries of the middle range.

    Table 2: Resources

    Antibodies
    SentencesResources
    In this antibody CMIA test, the SARS-CoV-2 antigen-coated paramagnetic microparticles bind to the IgG antibodies that attach to the SARS-CoV-2 spike protein (SP) in patients’ serum and plasma sample and it requires a minimum of 100 μl of serum or plasma.
    IgG
    suggested: None
    SARS-CoV-2 spike protein
    suggested: None

    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:
    This study has several limitations. First, given the observational design, there is potential for unmeasured confounding factors. In particular, participants in this study were individuals who elected to have a serology test for SARS-CoV-2 during the study period, many of them as part of a survey. Individuals may have variable reasons for accepting or refusing the offered serology test, which may have affected the results of this survey. Additionally, even though we adjusted our results for known factors that could affect antibody production and decay, additional factors may have affected the results. The BNT162b2 mRNA COVID-19 vaccine has been shown to stimulate production of antibodies to several SARS-CoV-2 proteins, not just the spike protein, suggesting that the vaccine provides short-term protection against variant strains(Amanat et al., 2021; Turner et al., 2021b). Combining these results with ours suggests that the recent surge in breakthrough infections in fully vaccinated individuals is due at least in part to declining levels of antibodies and not solely due to the variant strains of SARS-CoV-2. In a recent single-center, prospective, cross-sectional cohort study, children’s immunity was found to decline 4 months after the COVID-19 infection(Breuer et al., 2021). Lyer et al. reported that anti-S-protein antibodies reserved neutralizing abilities and persevered for up to 75 days after SARS-CoV-2 infection in >95% of patients(Iyer et al., 2020). Gudbjartsson et al. sh...

    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.
    • 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 10.1101/2021.08.19.21262111 on medRxiv