Evolution of Anti-SARS-CoV-2 IgG Antibody and IgG Avidity Post Pfizer and Moderna mRNA Vaccinations

  1. Kevin P. Bliden
  2. Tiancheng Liu
  3. Deepika Sreedhar
  4. Jessica Kost
  5. Jessica Hsiung
  6. Su Zhao
  7. Dingying Shan
  8. Abira Usman
  9. Naval Walia
  10. Alastair Cho
  11. Christophe Jerjian
  12. Udaya S. Tantry
  13. Paul A. Gurbel
  14. Meijie Tang
  15. Hongjie Dai

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Abstract

Messenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) are highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is uncertainty about the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in the immune responses between vaccines. Here we performed a prospective pilot study of 71 previously COVID-19 free subjects upon receiving both doses of either the Pfizer ( n = 54) or Moderna ( n = 17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibodies were measured longitudinally using a qualitative finger stick MidaSpot™ rapid test at the point-of-care for initial screening and a quantitative dry blood spot-based pGOLD™ laboratory test over ∼ four months post-vaccination. The average anti-RBD IgG antibody levels peaked at ∼ two weeks after the second dose of the vaccine and declined thereafter, while antibody avidity increased, suggesting antibody maturation. Moderna vaccine recipients compared to Pfizer vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels, and higher avidity up to the 90 days period. Differences in antibody levels diminished at ∼ 120 days post-vaccination, in line with the similar efficacy observed in the two vaccines. The MidaSpot™ rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts post full vaccination but turned negative greater than 90 days post-vaccination for 5.4% of subjects in the Pfizer cohort, whose quantitative anti-IgG were near the minimum levels of the group. Immune responses were found to vary greatly among vaccinees. Personalized longitudinal monitoring of antibodies could be necessary to assess the immunity duration of vaccinated individuals.

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  1. ScreenIT

    SciScore for 10.1101/2021.06.28.21259338: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Prospective study design: The study (NCT# 04910971) was performed in accordance with standard ethical principles and approved by the LifeBridge Health local Institutional Review Board under Protocol # 1707882.
    Consent: All participants provided written consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For comparative analysis, anti-RBD IgG and anti-NCP antibody data in a cohort of healthy volunteers from the pre-pandemic era (n = 200), and COVID-19 patients hospitalized (n = 34) from a previous study (NCT# 04493307) confirmed by positive reverse transcription polymerase chain reaction (RT-PCR) tests were included.
    anti-RBD IgG
    suggested: None
    anti-NCP
    suggested: None
    A mixture of diluted anti-RBD IgG/IgM purified antibodies as signal normalizer was loaded into the neighboring well on the same row as each sample tested, and a blank control (10% FBST only) was included on each biochip; 3) Secondary antibody incubation: each well was subsequently incubated with a mixture of 4 nM iFluor™820-labeled anti-human IgG secondary antibody, 4 nM CF647-labeled anti-human IgM secondary antibody, and 4 nM iFluor™820-labeled streptavidin in a 2% BSA solution for 30 minutes at room temperature.
    anti-RBD IgG/IgM
    suggested: None
    Recombinant DNA
    SentencesResources
    Avidity is always below the value of 1, since the denaturing urea tends to weaken antibody binding to antigens immobilized on pGOLD™.
    pGOLD™
    suggested: None
    Software and Algorithms
    SentencesResources
    Definitions: ROC (receiver operating characteristics) curve analysis was performed based on the quantification of antibody levels of pre-pandemic healthy subjects, vaccinees, and COVID-19 patients by MedCalc 20 (MedCalc Software Ltd, Ostend, Belgium).
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)
    A p value < 0.05 was considered statistically different between two groups (COVID-19, pre-vaccination D0, D19-28, D33-55, D61-83, D89-108, and D112-146) in this study (OriginPro 2021b, OriginLab Corporation, Northampton, Massachusetts, USA).
    OriginPro
    suggested: None
    OriginLab Corporation
    suggested: (Origin, RRID:SCR_014212)

    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:
    Limitations of our current study include the small sample size that is unequal among groups, missing data at some timepoints, and the limited population diversity.

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

    IdentifierStatusTitle
    NCT04910971RecruitingQuantification of Binding and Neutralizing Antibody Levels i…

    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 10.1101/2021.06.28.21259338v1 on medRxiv