A Prospective Randomised, Controlled Trial Switching Sirolimus For Mycophenolate To Enhance Immunological Responses To Third Dose Covid-19 Vaccination In Kidney Transplant Recipients With Poor Baseline Humoral Immunity
1Central and Northern Adelaide Renal and Transplant Services, Royal Adelaide Hospital, Adelaide, Australia, 2School of Biological Sciences, University of Adelaide, Adelaide, Australia, 3Basil Hetzel Institute, University of Adelaide, Adelaide, Australia, 4University of Sydney, Lilyfield, Ne, Australia, 5Kidney Node Laboratory, Charles Perkins Centre, The University of Sydney, The University of Sydney, Australia, 6School of Medical Sciences, University of Adelaide, Adelaide, Australia, 7Department of Immunology, Royal Adelaide Hospital, Adelaide, Australia, 8Department of Nephrology, Royal Prince Alfred Hospital, Sydney, Australia
Meeting: 2022 American Transplant Congress
Abstract number: 9088
Keywords: COVID-19, Rapamycin, Sirolimus (SLR), Vaccination
Topic: Clinical Science » Kidney » 38 - Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Information
Session Name: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Kidney transplant recipients (KTR) have inadequate responses to 2-dose COVID vaccination schedules and are at increased risk of severe COVID-19. Formation of T cell memory following vaccination is regulated by mTOR complex 1. mTOR inhibitors have been used in pre-clinical models to boost vaccine-elicited cytotoxic T cell memory responses. In observational studies, KTR receiving mTOR inhibitors had improved serological neutralisation and SARS-CoV-2 reactive T cell responses to 2 doses of COVID-19 vaccine, including cytotoxic T cells and circulating T follicular helper cells. We performed a clinical trial in stable KTR using sirolimus as a substitute for mycophenolate prior to a 3rd dose of COVID-19 vaccine to enhance COVID-19 vaccine responses.
*Methods: KTR receiving tacrolimus, mycophenylate and corticosteroid with inadequate response to 2 doses of a COVID vaccine (defined by anti-RBD IgG <100U/mL) and no history of COVID infection were recruited from 2 Australian transplant centres. Patients were randomised in a 1:1 ratio to continue mycophenolate maintenance or switch to sirolimus (trough level target 6 ng/mL). All patients received a 3rd dose of BNT162b2 COVID-19 vaccine and had immunological responses measured 4-6 weeks later.
*Results: 54 patients were randomised to sirolimus switch (n = 28), or control (n = 26). Patients were 70% male, mean age 57.5 years (SD10.4), with mean graft age 6.2 years (SD 5.4). Mean serum trough concentrations of sirolimus and tacrolimus were 6.4 and 6.1 respectively. There have been no safety or tolerability issues in the sirolimus cohort with stable serum creatinine (mean 117.8 vs 119.3, p=0.6), and mild increase in urinary ACR (mean 5.4 vs 17.4, p=0.1). Final results including immunological testing will be collated March 2022.
*Conclusions: Sirolimus switch is safe and well-tolerated. This trial will determine whether the strategy of mTOR inhibitor therapy peri-vaccination can optimise vaccine immune responses against COVID-19 in KTR.
To cite this abstract in AMA style:
Tunbridge MJ, Perkins G, Salehi T, Grubor-Bauk B, Sim B, Ying T, Singer JJ, Barry SC, Hissaria P, Chadban S, Coates PT. A Prospective Randomised, Controlled Trial Switching Sirolimus For Mycophenolate To Enhance Immunological Responses To Third Dose Covid-19 Vaccination In Kidney Transplant Recipients With Poor Baseline Humoral Immunity [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/a-prospective-randomised-controlled-trial-switching-sirolimus-for-mycophenolate-to-enhance-immunological-responses-to-third-dose-covid-19-vaccination-in-kidney-transplant-recipients-with-poor-baselin/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress