mTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients

Sunjae Bae, Jennifer L. Alejo, Teresa P.Y. Chiang, William A. Werbel, Aaron A.R. Tobian, Linda W. Moore, Ashrith Guha, Howard J. Huang, Richard J. Knight, A. Osama Gaber, R. Mark Ghobrial, Mara A. McAdams-DeMarco, Dorry L. Segev

Research output: Contribution to journalArticlepeer-review

Abstract

A recent study concluded that SARS-CoV-2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression- and machine learning-based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.090.130.18). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.001.452.13); however, importantly, this seemingly protective tendency disappeared (aOR = 0.470.731.12) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF-free regimens were associated with higher odds of positive antibody response (aOR = 2.394.267.92 for mTORi+tacrolimus; 2.345.5415.32 for mTORi-only; and 6.7810.2515.93 for tacrolimus-only), whereas MMF-including regimens were not, regardless of mTORi use (aOR = 0.811.542.98 for MMF + mTORi; and 0.811.512.87 for MMF-only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.

Original languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - 2022

Keywords

  • clinical research/practice
  • immunosuppressant
  • immunosuppression/immune modulation
  • infection and infectious agents
  • infection and infectious agents—viral: SARS-CoV-2/COVID-19
  • infectious disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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