Vaccination Response Modulation With a Targeted Rapamycin Protocol Study

Inclusion Criteria: * End-stage kidney disease requiring in-centre haemodialysis three times per week as kidney replacement therapy * Aged \>60 years Exclusion Criteria: * Aged \<60 years * Alternative haemodialysis regimens (e.g. twice-weekly haemodialysis, second-daily home haemodialysis) * Recent infection (\<6 months) with proven Influenza A, Influenza B, or RSV * Current use of immunosuppressive medications, including: * Oral steroid at a dose equivalent of 5 mg/day prednisolone or greater * Mycophenolate mofetil * Azathioprine * Calcineurin inhibitors * mTOR inhibitors * Recent use of intravenous immunosuppressive medications (\<6 months), including: * T-cell depleting agents (e.g. anti-thymocyte globulin) * B-cell depleting agents (e.g. rituximab) * Cyclophosphamide * Has a history of problems with side-effects associated with sirolimus use including * Angioedema * Active/recent opportunistic infection * Current or prior interstitial lung disease, non-infectious pneumonitis, organising pneumonia, or pulmonary fibrosis * Clinically significant pleural effusion or pericardial effusion * Active non-healing wounds, chronic skin ulcers, or planned major surgery/procedures * Current malignancy or recent malignancy with high recurrence risk * Severe or uncontrolled hyperlipidaemia * History of rhabdomyolysis * Severe hepatic impairment * Ongoing use of strong CYP3A4/P-gp inhibitors or inducers including * Inhibitors: Ketoconazole, Voriconazole, Itraconazole, Telithromycin, Clarithromycin * Inducers: Rifampicin, Rifabutin * Unable or unwilling to provide informed consent to participate in the trial * Known allergy to or intolerance of sirolimus (rapamycin) or the contents of the influenza or RSV vaccine