Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

  1. David J Sullivan
  2. Massimo Franchini
  3. Michael J. Joyner
  4. Arturo Casadevall
  5. Daniele Focosi

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Abstract

The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID- 19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody (nAb) titer units. In this analysis we systematically reviewed Omicron-neutralizing plasma activity data, and found that approximately 47% (424/902) of CCP from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geomean of geometric mean titers for 50% neutralization GM(GMT 50 ) of about 13, representing a more than 20-fold reduction from WA-1 neutralization. Two doses of mRNA vaccines in nonconvalescent subjects had a similar 50% percent neutralization with Omicron BA.1 neutralization GM(GMT( 50 )) of about 27. However, plasma from vaccinees recovered from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT( 50 )) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had GM(GMT 50 ) over 450 for BA.4/5 and over 1500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that defeat therapeutic monoclonal antibodies.

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  1. Version published to 10.1101/2021.12.24.21268317v6 on medRxiv
  2. Version published to 10.1101/2021.12.24.21268317v5 on medRxiv
  3. Version published to 10.1101/2021.12.24.21268317v4 on medRxiv
  4. Version published to 10.1101/2021.12.24.21268317v3 on medRxiv
  5. ScreenIT

    SciScore for 10.1101/2021.12.24.21268317: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    On December 22, 2021, we searched PubMed, medRxiv and bioRxiv for research investigating the efficacy of COVID19 convalescent plasma (either from vaccinated or unvaccinated donors) against SARS-CoV-2 VOC Omicron.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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.

  6. Version published to 10.1101/2021.12.24.21268317v2 on medRxiv
  7. Version published to 10.1101/2021.12.24.21268317v1 on medRxiv