Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients

  1. Andrew H. Karaba
  2. Jake D. Kim
  3. Teresa P-Y Chiang
  4. Jennifer L. Alejo
  5. Aura T. Abedon
  6. Jonathan Mitchell
  7. Amy Chang
  8. Yolanda Eby
  9. Trevor Scott Johnston
  10. Tihitina Aytenfisu
  11. Casey Hussey
  12. Alexa Jefferis
  13. Nicole Fortune
  14. Rivka Abedon
  15. Letitia Thomas
  16. Daniel S. Warren
  17. Ioannis Sitaras
  18. Andrew Pekosz
  19. Robin K. Avery
  20. Allan B. Massie
  21. William A. Clarke
  22. Aaron A.R. Tobian
  23. Dorry L. Segev
  24. William A. Werbel

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Abstract

Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS-CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and post-injection samples between 1/10/2022-4/4/2022. Binding antibody (anti-receptor binding domain [RBD], Roche) and surrogate neutralization (%ACE2 inhibition; ≥20% connoting neutralizing inhibition, Meso Scale Discovery) were measured against variants including Omicron sublineages BA.1 and BA.2. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and McNemar’s test. Among 61 participants, median (IQR) anti-RBD increased from 424 (IQR <0.8-2322.5) to 3394.5 (IQR 1403.9-7002.5) U/ml post T+C (p<0.001). The proportion demonstrating vaccine strain neutralizing inhibition increased from 46% to 100% post-T+C (p<0.001). BA.1 neutralization was low and did not increase (8% to 16% of participants post-T+C, p=0.06). In contrast, BA.2 neutralization increased from 7% to 72% of participants post-T+C (p<0.001). T+C increased anti-RBD levels, yet BA.1 neutralizing activity was minimal. Encouragingly, BA.2 neutralization was augmented and in the current variant climate T+C PrEP may serve as a useful complement to vaccination in high-risk SOTRs.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.24.22275467: (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

    Antibodies
    SentencesResources
    anti-SARS-CoV-2-S anti-receptor binding domain (RBD) pan immunoglobulin assay (units/mL, approximately 1:1 with World Health Organization binding antibody units [BAU]).
    anti-SARS-CoV-2-S anti-receptor binding domain ( RBD
    suggested: None
    Additionally, the Meso Scale Diagnostics (MSD, Rockville, MD) research assay was used to measure anti-RBD and anti-nucleocapsid (anti-N) binding antibody via the V-PLEX COVID-19 Respiratory Panel 3 Kit at 1:5000 dilution per manufacturer’s protocol.
    anti-RBD
    suggested: None
    anti-nucleocapsid
    suggested: None
    anti-N
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted on Stata/SE 17.0 (College Station, TX) and Microsoft Excel (2019).
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)

    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: We detected the following sentences addressing limitations in the study:
    A limitation of this study is that includes a small, heterogeneous sample. While this study aims to capture the real-life efficacy of T+C, the true effect of T/C is difficult to capture due to confounding factors from varying vaccination timeline, SARS-CoV-2 infection status, and other monoclonal antibody injections. Another limitation is the lack of long-term follow-up to assess rates of clinical breakthrough and safety. The study relied on participant surveys sent out a week after T+C doses and unsolicited patient self-reported to assess the safety and clinical breakthrough. Considering that preliminary safety and breakthrough data revealed events months after injections, future studies should be conducted on the long-term safety and breakthrough rate of T+C, particularly in SOTRs as their interaction with T+C has been understudied. T+C is a reasonable complementary strategy to vaccination in high-risk SOTRs to improve neutralizing capacity against select Omicron sublineages. Assessment of the real-world efficacy and safety of T+C in SOTR is of utmost importance, since SOTRs face heightened risks of severe illness or death from COVID-19 and since only few SOTRs were included in the PROVENT trial. Studies such as ours incorporating both clinical and laboratory data offer valuable insights into the real-world efficacy and safety of T+C in one of our most vulnerable population. Further research examining the durability of neutralization against emerging Omicron sublineages is ...

    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.

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  2. Version published to 10.1101/2022.05.24.22275467 on medRxiv