| Autor: |
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 Mekonnen, Pablo Garcia-Valtanen, Svjetlana Kireta, Julie K. Johnston, Christopher J. Drogemuller, Beatrice Z. Sim, Shane M. Spencer, Benedetta C. Sallustio, Iain Comerford, George Bouras, Daniela Weiskopf, Alessandro Sette, Anupriya Aggarwal, Vanessa Milogiannakis, Anouschka Akerman, Stuart Turville, Plinio R. Hurtado, Tracey Ying, Pravin Hissaria, Simon C. Barry, Steven J. Chadban, Branka Grubor-Bauk, P. Toby Coates |
| Rok vydání: |
2023 |
| Popis: |
Inadequate immune response to vaccination is a long-standing problem faced by immunosuppressed kidney transplant recipients (KTRs), requiring novel strategies to improve vaccine efficacy. In this study, the potential of mechanistic target of rapamycin inhibitors (mTORi) to improve T cell responses to COVID-19 vaccination was investigated. Following primary vaccination with adenoviral (ChAdOx1) or mRNA (BNT162b2) COVID-19 vaccines, KTRs receiving rapamycin demonstrated T cell responses greater than those of healthy individuals, characterized by increased frequencies of vaccine-specific central memory, effector memory and TEMRAT cells, in both the CD4+and CD8+compartments. Relative to standard-of-care triple therapy, mTORi-based therapy was associated with a 12-fold greater functional T cell response to primary vaccination of KTRs. The use of rapamycin to augment T cell responses to COVID-19 booster (third dose) vaccination was next investigated in a randomized, controlled trial. Immunosuppression modification with rapamycin was feasible and well-tolerated, but did not improve vaccine-specific T cell responses in this cohort. To understand the parameters for effective use of rapamycin as a vaccine adjuvant, mice were treated with rapamycin before primary or booster vaccination with ancestral and/or Omicron COVID-19 vaccines. Supporting the findings from KTRs, significant enhancement of functional and stem-like memory T cell responses was observed when rapamycin was administered from the time of primary, rather than booster, vaccination. Collectively, a positive effect of mTOR inhibitors on vaccine-induced T cell immunity against COVID-19 in humans was demonstrated.One Sentence SummaryRapamycin use at the time of primary COVID-19 vaccination augments the formation of functional, vaccine-specific T cell memory in immunosuppressed kidney transplant recipients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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