mTOR inhibition improves the formation of functional T cell memory following COVID-19 vaccination of kidney transplant recipients

• DOI: 10.1101/2023.03.27.23287773
• Publication Date: 2023-03-29T17:18:05Z
• Authors: Griffith B. Perkins; Matthew J. Tunbridge; Cheng Sheng Chai; Christopher M. Hope; Arthur Eng Lip Yeow; Tania Salehi; Julian Singer; Bree Shi; Makutiro G. Masavuli; Zelalem Addis Mek...; Pablo Garcia-Valt...; Svjetlana Kireta; Julie K. Johnston; Christopher J. Dr...; Beatrice Z. Sim; Shane M. Spencer; Benedetta C. Sall...; Iain Comerford; George Bouras; Daniela Weiskopf; Alessandro Sette; Anupriya Aggarwal; Vanessa Milogiann...; Anouschka Akerman; Stuart Turville; Plinio R. Hurtado; Tracey Ying; Pravin Hissaria; Simon C. Barry; Steven J. Chadban; Branka Grubor-Bauk; P. Toby Coates
• Keywords: Immunosuppression; Booster (rocketry)

Abstract Inadequate immune response to vaccination is a long-standing problem faced by immunosuppressed kidney transplant recipients (KTRs), requiring novel strategies improve vaccine efficacy. In this study, the potential of mechanistic target rapamycin inhibitors (mTORi) T cell responses COVID-19 was investigated. Following primary with adenoviral (ChAdOx1) or mRNA (BNT162b2) vaccines, KTRs receiving demonstrated greater than those healthy individuals, characterized increased frequencies vaccine-specific central memory, effector memory and EMRA cells, in both CD4 + CD8 compartments. Relative standard-of-care triple therapy, mTORi-based therapy associated 12-fold functional KTRs. The use augment booster (third dose) next investigated randomized, controlled trial. Immunosuppression modification feasible well-tolerated, but did not cohort. To understand parameters for effective as adjuvant, mice were treated before ancestral and/or Omicron vaccines. Supporting findings from KTRs, significant enhancement stem-like observed when administered time primary, rather booster, vaccination. Collectively, positive effect mTOR on vaccine-induced immunity against humans demonstrated. One Sentence Summary Rapamycin at augments formation functional, recipients.