Maintenance immunosuppressive therapy with everolimus preserves humoral immune responses

Kidney Int. 2010 Nov;78(9):934-40. doi: 10.1038/ki.2010.269. Epub 2010 Aug 11.


While the guidelines for vaccination in renal transplant recipients recommend the use of pneumococcal polysaccharide (PPS) and tetanus toxoid (TT), their efficacy in immunocompromised renal transplant recipients is not known. Here we tested the effect of everolimus on immune responses after vaccination by measuring the capacity of 36 stable renal transplant recipients to mount cellular and humoral responses after vaccination. Twelve patients in each treatment arm received immunosuppressive therapy consisting of prednisolone (P) plus cyclosporine (CsA), mycophenolate sodium (MPA), or everolimus. Patients were vaccinated with the T-cell-dependent antigens immunocyanin and TT, and the T-cell-independent PPS. Treatment with CsA partially inhibited and MPA completely abolished the capacity to mount a primary humoral response, whereas everolimus left this largely intact. Recall responses were inhibited by MPA only. All drug combinations inhibited cellular responses against TT. In patients treated with MPA, B-cell numbers were severely reduced. Thus, combined with P, treatment with MPA completely disturbed primary and secondary humoral responses. Everolimus or CsA allowed the boosting of T-cell-dependent and -independent secondary humoral responses. Treatment with everolimus allowed a primary response.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Aged
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Cyclosporine / therapeutic use
  • Cytokines / metabolism
  • Drug Therapy, Combination
  • Everolimus
  • Female
  • Hemocyanins / administration & dosage*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects*
  • Immunoglobulin G / blood
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Netherlands
  • Pneumococcal Vaccines / administration & dosage*
  • Prednisolone / therapeutic use
  • Prospective Studies
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tetanus Toxoid / administration & dosage*
  • Time Factors
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Cytokines
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Pneumococcal Vaccines
  • Tetanus Toxoid
  • Cyclosporine
  • Hemocyanins
  • Everolimus
  • Prednisolone
  • keyhole-limpet hemocyanin
  • Mycophenolic Acid
  • Sirolimus