Humoral immune responses against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine

  1. Kapil K. Saharia
  2. Jennifer S. Husson
  3. Silke V. Niederhaus
  4. Thierry Iraguha
  5. Stephanie V. Avila
  6. Youngchae J. Yoo
  7. Nancy M. Hardy
  8. Xiaoxuan Fan
  9. Destiny Omili
  10. Alice Crane
  11. Amber Carrier
  12. Wen Y. Xie
  13. Erica Vander Mause
  14. Kim Hankey
  15. Sheri Bauman
  16. Patricia Lesho
  17. Heather D. Mannuel
  18. Ashish Ahuja
  19. Minu Mathew
  20. James Avruch
  21. John Baddley
  22. Olga Goloubeva
  23. Kirti Shetty
  24. Saurabh Dahiya
  25. Aaron P. Rapoport
  26. Tim Luetkens
  27. Djordje Atanackovic

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Solid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants.

Methods

We performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants.

Results

Prior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant.

Conclusions

Only a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.12.29.21268529: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was reviewed and approved by the University of Maryland (Baltimore) institutional review board (HP-00095043).
    Consent: For that study, informed consent was obtained and blood samples were collected under IRB HP-00091425.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were washed as described above before incubation with secondary antibodies against pan-human IgG (Southern Biotech, Cat. No. 2040-04) or IgA (Southern Biotech, Cat. No. 2050-04).
    pan-human IgG
    suggested: None
    For non-SARS-CoV-2 antigens, serum dilutions for anti-GST (glutathione-S-transferase) antibodies (Supplemental Table 1) were used as a negative control.
    anti-GST
    suggested: None
    glutathione-S-transferase
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses: Statistical analyses for serological analyses were performed using GraphPad Prism 9 software (GraphPad Software, San Diego, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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 10.1101/2021.12.29.21268529v1 on medRxiv
  3. Version published to 10.1002/cti2.1391