Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralizing antibodies in vaccinated solid organ transplant recipients

  1. Chih-Chao Chang
  2. George Vlad
  3. Elena Rodica Vasilescu
  4. Ping Li
  5. Syed A. Husain
  6. Elaine A. Silvia
  7. David J Cohen
  8. Lloyd E. Ratner
  9. Wei-Zen Sun
  10. Sumit Mohan
  11. Nicole Suciu-Foca

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Abstract

The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). Although a 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, its effectiveness was still largely unknown. We analyzed 113 vaccinated SOTRs, and 30 healthy controls (HCs), some of whom had recovered from COVID, for their immune responses against the original vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant. Here, we report that 3 doses of the mRNA vaccine had only a modest effect in eliciting anti-viral responses against all viral strains in the fully vaccinated SOTRs who did not contract the virus. Only 34.0% (16/47) of this group of patients demonstrated both detectable anti-RBD IgG and neutralization activities against alpha, beta, and delta variants, and only 8.5% (4/47) of them showed additional omicron-neutralizing capacities. In contrast, 79.5% (35/44) of the vaccinated recovered-SOTRs demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. These findings illustrate a significant impact of previous infection on the development of anti-COVID immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

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  1. ScreenIT

    SciScore for 10.1101/2022.04.13.22273829: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 2.1 Human Subjects, Patients Privacy Protection: This retrospective study was approved by a protocol (AAAT3602) from the Institutional Review Board at Columbia University Irving Medical Center (CUIMC).
    Consent: Verbal informed consent was given by HCs.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The other group, (COVID-naïve SOTR, n = 69), were those who had not been infected, and were confirmed as seronegative for anti-nucleocapsid IgG antibodies.
    anti-nucleocapsid IgG
    suggested: None
    The positivity of anti-viral IgG antibodies was pre-set by manufacturer as equal to or above 700 MFI.
    anti-viral IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2’s pseudoviral particles were prepared from transfection of 293T cells with lentiviral packing plasmids, together with various SARS-CoV-2 Spike coding plasmids, according to a method described by Crawford16 et al.
    293T
    suggested: None
    Each well was pre-seeded with 1.5×104 293T-ACE2 cells in 60 µl medium (DMEM supplemented with 10% FCS) in the presence of 8 µg/ml polybrene.
    293T-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    (alpha variant, #170451), pcDNA3.3_CoV2_501V2 (1.351, beta variant, #170449), pcDNA3.3-SARS2-B.1.617.2 (delta variant, #172320) and pTwist-SARS-CoV-2 Δ18 B.1.1.529 (Omicron variant, #179907).
    pcDNA3.3_CoV2_501V2
    suggested: RRID:Addgene_170449)
    pcDNA3.3-SARS2-B.1.617.2
    suggested: RRID:Addgene_172320)
    The following plasmids were obtained from Bei Resources: pHDM-SARS-CoV-2-SpikeD614G (NR-53765), Lenti-pseudoviral packing plasmids, pHAGE-CMV-Luc2-IRES-ZsGreen-W (NR-52516), pHDM-Hgpm2 (NR-52517), pHDM-tatt11b (NR-52518) and pRC-CMV-rev1b (NR-52519).
    pHAGE-CMV-Luc2-IRES-ZsGreen-W
    suggested: RRID:Addgene_164432)
    pRC-CMV-rev1b
    suggested: RRID:Addgene_164443)
    Software and Algorithms
    SentencesResources
    2.6 Multiplexed magnetic bead-based assay for detection of neutralizing antibodies against the vaccine strain or VOC: Bio-Rad’s Bio-Plex Pro® Human SARS-CoV-2 Neutralization Assay was used for detection of neutralization activities with some modifications.
    VOC
    suggested: (Queensland University of Technology Central Analytical Research Facility (CARF Proteomics and Small Molecule Mass Spectrometry Core Facility, RRID:SCR_017933)
    Bio-Rad’s
    suggested: None
    Bio-Plex
    suggested: None
    Data (mean fluorescence intensity, MFI) were acquired using xPONENT® Software and analyzed with Microsoft’s Excel Software.
    Microsoft’s Excel
    suggested: None
    2.7 Statistics: Statistical analyses and generation of the graphs were carried out using GraphPad Prism 9.0.
    GraphPad Prism
    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 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 10.1101/2022.04.13.22273829v1 on medRxiv
  3. Version published to 10.1002/cti2.1411