Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate

  1. Amin Addetia
  2. Katharine H. D. Crawford
  3. Adam Dingens
  4. Haiying Zhu
  5. Pavitra Roychoudhury
  6. Meei-Li Huang
  7. Keith R. Jerome
  8. Jesse D. Bloom
  9. Alexander L. Greninger

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Abstract

The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have been performed only in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral reverse transcription-PCR (RT-PCR) testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.13.20173161: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the University of Washington Institutional Review Board.
    RandomizationThe strains were then stratified by Pangolin lineage (A or B) (https://github.com/cov-lineages/pangolin) and 49 from lineage A and 59 from lineage B were randomly selected along with the Wuhan-Hu-1 reference genome (NC_045512.2) (25).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Neutralization Assays and Anti-Spike Antibody Testing: The presence of anti-Spike and neutralizing antibodies was analyzed in pre-departure sera samples from individuals that were positive in the Abbott assay screening through four different methods: Spike IgG ELISA, RBD ELISA, ACE2 blockade of binding ELISA, and pseudovirus neutralization.
    Anti-Spike
    suggested: None
    Pooled sera collected from 2017-2018 from 75 individuals (Gemini Biosciences, 100-110, lot H86W03J) and CR3022 antibody (starting at 1/ug/mL, also diluted 4-fold) were included as negative and positive controls, respectively.
    CR3022
    suggested: (Imported from the IEDB Cat# CR3022, RRID:AB_2848080)
    Plates were again washed three times, and then 50μL of a 1:300 dilution of goat anti-human IgG-Fc horseradish peroxidase (HRP)-conjugated antibody (Bethyl Labs, A80-104P) in PBS-T containing 1% milk was added to each well and incubated for 1 hour at room temperature.
    anti-human IgG-Fc
    suggested: (Bethyl Cat# A80-104P, RRID:AB_67064)
    Software and Algorithms
    SentencesResources
    Clinical testing of serum samples was performed using the Abbott Architect SARS-CoV-2 IgG assay (20).
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Sequencing reads are available at NCBI BioProject PRJNA610428 and sequence accessions are available in Supplemental Table 1.
    BioProject
    suggested: (NCBI BioProject, RRID:SCR_004801)
    Briefly, sequencing reads were adapter- and quality-trimmed with BBDuk and mapped to the SARS-CoV-2 reference genome (NC_045512.2) using Bowtie 2 (23).
    Bowtie
    suggested: (Bowtie, RRID:SCR_005476)
    Reads aligning to the SARS-CoV-2 reference genome were filtered using BBDuk and assembled with SPAdes (24).
    SPAdes
    suggested: (SPAdes, RRID:SCR_000131)
    For samples that did not produce a genome through the automated pipeline, the mapped read assemblies were visualized in Geneious and a consensus genome was called manually.
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    Sequences were aligned with MAFFT v7.453 (26) and a phylogenetic tree was constructed using FastTree (version 2.1.1) (27) with the 5’ and 3’UTRs masked.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    FastTree
    suggested: (FastTree, RRID:SCR_015501)
    Strains most closely related to the major outbreak clade were identified by searching against a custom BLASTN database containing all SARS-CoV-2 sequences in GISAID (accessed August 3, 2020).
    BLASTN
    suggested: (BLASTN, RRID:SCR_001598)
    Neutralization Assays and Anti-Spike Antibody Testing: The presence of anti-Spike and neutralizing antibodies was analyzed in pre-departure sera samples from individuals that were positive in the Abbott assay screening through four different methods: Spike IgG ELISA, RBD ELISA, ACE2 blockade of binding ELISA, and pseudovirus neutralization.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    After calculating the fraction infectivity, we used the neutcurve Python package (https://jbloomlab.github.io/neutcurve/) to calculate the serum dilution that inhibited infection by 50% (IC50) by fitting a Hill curve with the bottom fixed at 0 and the top fixed at 1.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your data.

    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 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.

    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 10.1128/jcm.02107-20
  3. Version published to 10.1101/2020.08.13.20173161 on medRxiv