High but Short-lived anti-SARS-CoV2 neutralizing, IgM, IgA, and IgG levels among mRNA-vaccinees compared to naturally-infected participants

  1. Haissam Abou-Saleh
  2. Bushra Y. Abo-Halawa
  3. Salma Younes
  4. Nadin Younes
  5. Duaa W. Al-Sadeq
  6. Farah M. Shurrab
  7. Na Liu
  8. Hamda Qotba
  9. Nader Al-Dewik
  10. Ahmad H. Ismail
  11. Hadi M. Yassine
  12. Laith J. Abu-Raddad
  13. Gheyath K. Nasrallah

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Abstract

1.

Background

Waning of protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to waning of immunity to SARS-COV-2 remains unclear.

Aim

We aimed to investigate dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals.

Methods

We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n=100) at two phases: phase-I (P-I) at ∼1.4 and phase-II (P-II) at ∼5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n=40) at ∼1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured.

Results

VN group produced significantly greater antibody responses ( p <0.001) than NI group at P-I except for IgM. In VN group, a significant waning in antibody response was observed in all isotypes. There was about ∼ a 4-fold decline in NTAb levels ( p <0.001), anti-S-RBD-IgG (∼5-folds, p <0.001), anti-S-RBD-IgM (∼6-folds, p <0.001), and anti-S1-IgA (2-folds, p <0.001). In NI group, a significant but less steady decline was notable in NTAb (∼1-folds, p <0.001), anti-S-RBD IgG (∼1-fold, p =0.005), and S-RBD-IgM (∼2-folds, p <0.001). Unlike VN group, NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA levels which were ∼3 folds higher in VN subjects compared to NI in P-1 ( p <0.001), dropped to almost same levels, with no significant difference observed between the two groups in P-II.

Conclusion

While double dose mRNA vaccination boosted antibody levels, this “boost” was relatively short-lived in vaccinated individuals.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.08.22274817: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 3.1 Ethical approval and sample collection: The study was reviewed and approved by the Institutional Review Board at Qatar University (QU-IRB 1537-FBA/21).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Phosphate-buffered saline (PBS) was used to dilute the samples that presented readings higher than the mentioned range. (2) Antibodies to the RBD of the S1 subunit of the viral spike protein (IgG (S-RBD)) (catalog No. SARS-CoV-2 Anti-S-RBD IgG122, Mindray, China), with a cut off index for the kit is ≥ 10-1000 AU/ml, and WHO standardization factor of 1.15 BAU/mL.
    viral spike protein ( IgG
    suggested: None
    Anti-S-RBD IgG122
    suggested: None
    The results interpretation of Vidas IgM according to test index value (i): i < 1.00 Negative (IgM antibodies to SARS-CoV-2 not detected), i ≥ 1.00 Positive (IgM antibodies to SARS-CoV-2 detected).
    IgM
    suggested: None
    Architect automated chemiluminescent assay (Abbott Laboratories, USA) was used to test the samples for previous infection by measuring the SARS-CoV-2 anti-nucleoprotein IgG antibodies (anti-N), considering that the IgG antibodies produced against the RBD on the spike protein are different from the IgG antibodies produced against the nucleoprotein of the virus.
    IgG
    suggested: None
    Therefore, the positive anti-N results of SARS-CoV-2 anti-nucleoprotein IgG antibodies indicate previous exposure to the whole virus (17).
    anti-N
    suggested: None
    anti-nucleoprotein IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Architect automated chemiluminescent assay (Abbott Laboratories, USA) was used to test the samples for previous infection by measuring the SARS-CoV-2 anti-nucleoprotein IgG antibodies (anti-N), considering that the IgG antibodies produced against the RBD on the spike protein are different from the IgG antibodies produced against the nucleoprotein of the virus.
    Abbott Laboratories
    suggested: None
    3.3 Statistical analysis: GraphPad Prism software (version 9.3.1
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    , GraphPad Software, Inc.
    GraphPad
    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:
    This study had several limitations. First of all, it is noteworthy to mention that a variety of variables could influence the level of immune response elicited after infection. It should be noted that our NI group included only 45% symptomatic subjects, while the remaining were paucisymptomatic (20%), asymptomatic (20%), or with unspecified severity (15%), which could have affected our results. In those with more severe COVID-19, binding and NTAb antibody titers have been reported to rise faster and reach a greater peak [9, 10, 14]. Individuals with symptomatic SARS-CoV-2 infection have greater antibody titers than asymptomatic, and people who are hospitalized have higher antibody titers than people who are managed as outpatients [9, 10, 15, 16]. Furthermore, several studies have shown a link between cycle threshold (Ct) and antibody titer, with lower Ct values linked with greater antibody titers at the population level [9, 13]. These factors could have impacted the elicited immune response. Furthermore, we have not measured antibody levels prior to vaccine administration. Despite these limitations, this study has several strengths that merit attention. First, most of the published studies have mainly focused on IgG and IgM, whereas studies on NTAb antibodies, and IgA response are very limited, particularly among naturally infected unvaccinated subjects. Second, in this study, we assessed anti-N antibodies, which is crucial to identify those who had been exposed to a virus bu...

    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.

  2. Version published to 10.1101/2022.05.08.22274817 on medRxiv