Vaccination of solid organ transplant recipients previously infected with SARS-CoV2 induces potent responses that extend to variants, including Omicron

  1. Alok Choudhary
  2. Mark Lerman
  3. David Calianese
  4. Salman Khan
  5. Judson Hunt
  6. Afzal Nikaein
  7. Avi Z. Rosenberg
  8. Jonathan I. Silverberg
  9. Israel Zyskind
  10. William Honnen
  11. Dabbu K. Jaijyan
  12. Erica Kalu
  13. Abraham Pinter

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Abstract

Background

Multiple factors affecting COVID19 vaccine induced antibody responses in SARS-CoV2 uninfected immunosuppressed solid organ transplant recipients have been reported; however, there is still a lack of information on non-ACE2 competing cross-CoV2 neutralizing functional antibodies induced in these cohorts, and similarly the vaccine efficacy in prior CoV2-infected immunosuppressed individuals is not well understood.

Methods

COVID19 vaccine efficacy was compared in a panel of kidney and heart transplant recipients who were either CoV2 uninfected (n=63) or CoV2 infected (n=13) prior to receiving two or three doses of mRNA vaccines using pseudoviral neutralization assays against eight CoV2 strains (the CoV2_D614G ancestral strain, alpha, beta, gamma, delta, kappa, lambda, and omicron-BA1 variants), while plasma antibody titers were determined by ELISA using recombinant CoV2-RBD-wt proteins.

Results

Minimally protective neutralizing plasma antibody titers (IC 50 ≥ 1:50) against the variants were recorded 7-14% and 25-35% after the second and third doses respectively, with Omicron being the most resistant. In contrast, all previously infected vaccinees possessed minimal protective plasma titers against D614G after either two or three vaccine doses, with 11/13 exhibiting strong protection (IC50≥ 1:500) and 10/13 exceeding the minimal protective titer against Omicron. Absorption of the selected plasma with immobilized parental RBD removed ≥ 90% of its neutralizing activity, indicating that the dominant neutralization targets were in the RBD.

Conclusions

This study showed that CoV2 infection followed by vaccination, but not vaccination alone, induces the presence of potent highly cross-reactive CoV2 neutralizing plasma antibodies that extend to Omicron variants, even in immunosuppressed SOTRs.

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  1. Version published to 10.1101/2022.02.10.22270607v2 on medRxiv
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    SciScore for 10.1101/2022.02.10.22270607: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All the participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Alkaline phosphatase conjugated goat anti-human IgG, IgM and IgA detector antibodies (Jackson ImmunoResearch Laboratories) were diluted 1:2000 in 2% non-fat dry milk and added to the plates (50 ul/well) and incubated for one hr at 37°C.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    - plasmids into HEK 293 T cells, to produce the CoV2 psV.
    HEK 293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    HuACE2-HeLa cells were infected with the CoV2 psV in DMEM media supplemented with polybrene (10 ug/ml) and infectivity was determined by reading luciferase activity in the cell-lysate after 72 hrs post-infection upon adding luciferase substrate (Britelite, PE).
    HuACE2-HeLa
    suggested: None
    To determine the neutralization potency of the plasma psV dilutions giving ∼100,000 RLU were used to infect Hu-ACE2-HeLA cells in the presence of titrated plasma.
    Hu-ACE2-HeLA
    suggested: None
    Recombinant DNA
    SentencesResources
    In brief, a gene fragment of the CoV2-Spike gene encoding the RBD was synthesized commercially (IDT) and cloned at the 3’ end of a gene expressing the N-terminal fragment of the Friend ectotropic MuLV (Fr-MuLV) surface protein (SU) gp70 gene in the expression vector pcDNA3.4 (Addgene, Watertown, MA).
    pcDNA3.4
    suggested: RRID:Addgene_131198)
    CoV2 Pseudovirus (psV) preparation and ACE2-HeLa cell-based neutralization Assay: Codon optimized D614G, Alpha, Beta, Gamma, Delta, Kappa and Lambda spike gene sequences with 18 aa C-terminal truncations were cloned into the pCAGGS vector40.
    pCAGGS
    suggested: RRID:Addgene_127347)
    Software and Algorithms
    SentencesResources
    A280 measurements of purified proteins were acquired via Nanodrop and the final concentrations were derived with the molecular weight and extinction coefficient calculated online by ExPASy.
    ExPASy
    suggested: None
    2.5 Statistics: GraphPad Prism 8.0 software was used to calculate the mean, median, interquartile range (IQR) and determine suitable parametric or nonparametric tests to be applied for statistical analyses of the data.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Pearson’s coefficient and Spearman r value were calculated to identify positive and negative correlations and the neutralization potency of plasma, defined as the plasma dilution, required to reduce viral signal by 50% (IC50), were calculated using One-Site Fit LogIC50 regression in GraphPad Prism 8.0.
    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

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  3. Version published to 10.1101/2022.02.10.22270607v1 on medRxiv