Loss of Neutralizing Antibody Response to mRNA Vaccination against SARS-CoV-2 Variants: Differing Kinetics and Strong Boosting by Breakthrough Infection

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Abstract

The waning efficacy of SARS-CoV-2 vaccines combined with the continued emergence of variants resistant to vaccine-induced immunity has reignited debate over the need for booster vaccines. To address this, we examined the neutralizing antibody (nAb) response against four major SARS-CoV-2 variants—D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2)—in health care workers (HCWs) at pre-vaccination, post-first and post-second mRNA vaccine dose, and six months post-second mRNA vaccine dose. Neutralizing antibody titers against all variants, especially the Delta variant, declined dramatically from four weeks to six months post-second mRNA vaccine dose. Notably, SARS-CoV-2 infection enhanced vaccine durability, and mRNA-1273 vaccinated HCWs also exhibited ~2-fold higher nAb titers than BNT162b2 vaccinated HCWs. Together these results demonstrate possible waning of protection from infection against SARS-CoV-2 Delta variant based on decreased nAb titers, dependent on COVID-19 status and the mRNA vaccine received.

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  1. SciScore for 10.1101/2021.12.06.471455: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableThese 48 HCWs ranged in age from 22-61 years (median = 37; IQR = 31.75-43.25) and included 26 male and 22 female HCWs.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were then washed and treated with 100 μL of HRP labeled anti-human-IgG antibody (31220, EDI, San Diego, CA) for 30 min.
    anti-human-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell Lines and Maintenance: HEK293T cells (CRL-11268, CVCL_1926, ATCC, Manassas, VA) and HEK293T-ACE2 cells (NR-52511, BEI Resources, ATCC, Manassas, VA) were maintained in Dulbeco’s Modified Eagles Medium (Gibco, 11965-092, ThermoFisher Scientific, Waltham, MA) supplemented with 10% (v/v)
    HEK293T
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    CVCL_1926
    suggested: None
    To determine relative titers of harvested virus, the pseudotyped virus for each of the SARS-CoV-2 variants were used to infect HEK293T-ACE2 cells.
    HEK293T-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    Constructs for Pseudotyping Virus Production: Production of lentiviral pseudotyped virus was performed using a previously reported protocol using pNL4-3-HIV-1-inGluc vector (13, 14, 21–23).
    pNL4-3-HIV-1-inGluc
    suggested: None
    This vector is a pNL4-3-HIV-1 ΔEnv construct and contains a Gaussia luciferase reporter gene with a CMV promoter both oriented in an anti-sense orientation relative to the HIV-1 genome.
    pNL4-3-HIV-1 ΔEnv
    suggested: None
    Constructs encoding N- and C-terminal flag-tagged SARS-CoV-2 spike (S) for each variant — D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) — were synthesized and cloned into pcDNA3.1 vector using KpnI/BamHI restriction enzyme cloning by GenScript BioTech (Piscataway, NJ).
    pcDNA3.1
    suggested: RRID:Addgene_79663)
    Software and Algorithms
    SentencesResources
    Neutralizing titer 50% (NT50) for each serum sample was determined by non-linear regression with least squares fit in GraphPad Prism 5 (GraphPad Software, San Diego, California)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.