The Effect of Waning on Antibody Levels and Memory B Cell Recall following SARS-CoV-2 Infection or Vaccination

  1. David Forgacs
  2. Vanessa Silva-Moraes
  3. Giuseppe A. Sautto
  4. Hannah B. Hanley
  5. Jasper L. Gattiker
  6. Alexandria M. Jefferson
  7. Ravindra Kolhe
  8. Ted M. Ross

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Abstract

In order to longitudinally track SARS-CoV-2 antibody levels after vaccination or infection, we assessed anti-RBD antibody levels in over 1000 people and found no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, a significant waning of antibody levels was observed following vaccination. Participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to higher antibody levels, which were maintained at higher levels than in previously infected, unvaccinated participants. Older participants exhibited lower level of antibodies after vaccination, but a higher level after infection than younger people. The rate of antibody waning was not affected by pre-immunity or age. Participants who received a third dose of an mRNA vaccine not only increased their antibody levels ~14-fold, but also had ~3 times more antibodies compared to when they received their primary vaccine series. PBMC-derived memory B cells from 13 participants who lost all circulating antibodies were differentiated into antibody secreting cells (ASCs). There was a significant recall of memory B cell ASCs in the absence of serum antibodies in 5–8 of the 10 vaccinated participants, but not in any of the 3 infected participants, suggesting a strong connection between antibody levels and the effectiveness of memory B cell recall.

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  1. Version published to 10.3390/vaccines10050696
  2. ScreenIT

    SciScore for 10.1101/2022.03.16.484099: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: SPARTA participants: Eligible participants between 18 and 90 years old were enrolled starting in April 2020 with written informed consent in Athens and Augusta, GA, Memphis, TN, and Los Angeles, CA.
    IRB: The study procedures, informed consent, and data collection documents were reviewed and approved by the WIRB Copernicus Group Institutional Review Board (WCG IRB #202029060).
    Sex as a biological variableOf the ∼3,800 SPARTA enrolled participants, 1,081 were randomly selected to be included in this study (Table S1). 68.5% of them identified as females, and 31.4% as males.
    RandomizationOf the ∼3,800 SPARTA enrolled participants, 1,081 were randomly selected to be included in this study (Table S1). 68.5% of them identified as females, and 31.4% as males.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    IgG antibodies were detected using horseradish peroxidase (HRP)-conjugated goat anti-human IgG detection antibody (Southern Biotech, Birmingham, AL, USA) at a 1:4,000 dilution and colorimetric development was accomplished using 100 μL of 0.1% 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS, Bioworld, Dublin, OH, USA) solution with 0.05% H2O2 for 18 minutes at 37ºC.
    anti-human IgG
    suggested: None
    2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)
    suggested: None
    The conditioned cell culture supernatants were serially diluted to assess total and antigen-specific IgG antibody levels by ELISA.
    antigen-specific IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The USA-WA1/2020 SARS-CoV-2 strain (100 TCID50/50µl; NCBI accession number: PRJNA717311) was co-incubated with serially diluted serum samples for 1 hour at 37°C and then added to a monolayer of Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Samples were acquired on Agilent NovoCyte Quanteon and analyzed using FlowJo v10.2.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Comparison of the four groups (naïve unvaccinated, infected unvaccinated, naïve vaccinated, infected vaccinated) based on previous infection and vaccination as well as different timepoints were investigated by one-way ANOVA and paired t tests using GraphPad Prism 9.3.1 (RRID: SCR_002798).
    GraphPad Prism
    detected: 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:
    One of the limitations of this study is that we relied on accurate reporting of demographic information, comorbidities, previous SARS-CoV-2 testing and symptoms, and vaccine information by the participants. While the sample size for each of the four infected/vaccinated groups compared is robust, not all timepoints were available for all participants. Only participants who were convalescent prior to vaccination were reported in the infected vaccinated group, participants who had breakthrough infections after vaccination will be included in a future study. The sample size for the in vitro differentiation experiment was low due to the uncommon nature of losing seroprotective status amongst our participants. All participants who lost their confirmed seroprotected status were included in the analysis; future studies are necessary to strengthen our findings with additional participants. In conclusion, vaccinated groups seroconverted to higher antibody levels and experienced significant antibody waning regardless of pre-immunity. In contrast, infected unvaccinated participants had no significant waning during the first 14 months after infection. The rate of antibody waning was not significantly different between pre-immune and immunologically naïve participants. Antibody levels are greatly increased by the administration of a booster dose, to a level 3-fold higher than their previous peak antibody level 2-4 weeks after the second dose. Memory B cell recall responses were absent in a...

    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 10.1101/2022.03.16.484099v1 on bioRxiv