Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)–Specific Memory B Cells From Individuals With Diverse Disease Severities Recognize SARS-CoV-2 Variants of Concern

  1. Zoe L Lyski
  2. Amanda E Brunton
  3. Matt I Strnad
  4. Peter E Sullivan
  5. Sarah A R Siegel
  6. Fikadu G Tafesse
  7. Mark K Slifka
  8. William B Messer

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Abstract

The unprecedented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has called for substantial investigations into the capacity of the human immune system to protect against reinfection and keep pace with the evolution of SARS-CoV-2. We evaluated the magnitude and durability of the SARS-CoV-2–specific antibody responses against parental WA-1 SARS-CoV-2 receptor-binding domain (RBD) and a representative variant of concern (VoC) RBD using antibodies from 2 antibody compartments: long-lived plasma cell–derived plasma antibodies and antibodies encoded by SARS-CoV-2–specific memory B cells (MBCs). Thirty-five participants naturally infected with SARS-CoV-2 were evaluated; although only 25 of 35 participants had VoC RBD–reactive plasma antibodies, 34 of 35 (97%) participants had VoC RBD–reactive MBC-derived antibodies. Our finding that 97% of previously infected individuals have MBCs specific for variant RBDs provides reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to elicit immunity with the capacity to limit disease severity and transmission of VoCs as they arise and circulate.

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  3. Version published to 10.1093/infdis/jiab585
  4. ScreenIT

    SciScore for 10.1101/2021.05.28.21258025: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Human Research Ethics: The study was reviewed and approved by the Oregon Health & Science University Institutional Review Board (IRB# 21230).
    Consent: Informed consent was obtained from subjects on initiation of their participation in the study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were washed 4 times with wash buffer, and 100µL (plasma) or 50 μL (LDA) of 1:3000 dilution of anti-human IgG-HRP (BD Pharmingen, 555788) detection antibody was added and incubated at RT for 1 hour.
    anti-human IgG-HRP
    suggested: None
    For subjects with low frequency of antigen-specific antibody secreting cells frequency was determined by number of positive wells divided by the total number of IgG positive secreting wells, multiplied by one million, giving a frequency per million PBMCs stimulated.
    antigen-specific
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, His-tagged VoC-RBD bearing lentivirus was produced in HEK 293-T cells and used to infect HEK 293-F suspension cells.
    HEK 293-T
    suggested: None
    Software and Algorithms
    SentencesResources
    All analysis was done in Prism version 9.1.1.
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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:
    Breakthrough infections and the emergence of VoC highlight the limitations of SARS-CoV-2 S specific plasma antibodies alone to recognize and protect against VoC, and work by our group and others, [9, 28-30] has shown that serum or plasma antibodies elicited by natural infection are less potent overall against several VoC. However, serologic studies do not capture the antibodies that will be secreted by MBCs when they are stimulated, expand, and differentiate into a new population of antibody secreting cells. Here we characterized the SARS-CoV-2 specific MBC derived antibodies, with three critical findings: 1) SARS-CoV-2 RBD specific MBCs can be detected in asymptomatic, seronegative, PCR-positive subjects, 2) MBC populations elicited following primary infection appear relatively stable over time, up to nearly one-year post-infection, and 3) the antibodies these MBCs are programmed to secrete recognize both parental and VoC RBDs at roughly equivalent frequencies. These results are consistent with MBC studies of other pathogens that show MBCs retain pathogen specific antibody diversity that is different from LLPC-derived Abs [11-12, 31]. Because of this additional line of antibody defense latent in SARS-CoV-2 specific MBCs, we contend there is reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to limit disease severity and transmission of VoC as they inevitably emerge in the setting of ongoing transmission. The observation that the high ELI...

    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.

  5. Version published to 10.1101/2021.05.28.21258025v1 on medRxiv