Vaccination Response Modulation With a Targeted Rapamycin Protocol Study (VON TRAPP)

Vaccination Response Modulation With a Targeted Rapamycin Protocol (VON TRAPP) Study

This study will investigate dialysis recipients' responses to important vaccines.

Research suggests that a medication commonly used by transplant recipients may improve vaccine responses. The investigators will be conducting a clinical trial to see whether a short course of low-dose Sirolimus improves the response to vaccination against respiratory syncytial virus (RSV) and influenza (flu) in patient with kidney disease over 60 years old who receive haemodialysis.

Study Overview

• Status: Not yet recruiting
• Conditions: Older Adults; Vaccine Immune Response; Haemodialysis Patients
• Intervention / Treatment: Biological: Influenza vaccine (Sequiris Fluad Quad); Biological: RSV vaccine (Pfizer Abrysvo); Drug: Sirolimus (RAPAMUNE)

Detailed Description

Respiratory viruses are a significant cause of morbidity and mortality in Australia. Respiratory syncytial virus (RSV) and Influenza are major contributors to yearly respiratory virus epidemics that particularly affect older persons and persons with end-stage kidney disease.

Vaccination is available for the prevention of both RSV and Influenza, but unfortunately the conditions that confer a higher risk of morbidity and mortality with infection are also key predictors of poor responses to vaccination.

Effective vaccine responses require activation of both T and B cells to generate protective and long-lasting antibody and cellular immune responses. Immunosenescence from ageing and end-stage kidney disease, dampens antibody responses and impairs cellular immunity, rendering patients vulnerable to infection.

Previous research suggests that sirolimus(rapamycin)-based immunosuppression regimens improve vaccine immunogenicity. Sirolimus (rapamycin) is a potent inhibitor of mTORC1 which regulates memory CD8+ T cells. Targeting mTORC1 has previous been shown to improve vaccination response in humans to influenza. More recently, small studies have suggested improved responses to COVID vaccination in kidney transplant recipients switched to sirolimus (rapamycin)-based regimens.

This study will investigate a role for sirolimus (rapamycin) as a peri-vaccination immune modulation therapy. The VON TRAPP study is a phase 2a randomised clinical trial that aims to define the optimal, practical and tolerable regimen of peri-vaccination sirolimus (rapamycin) administration to positively modify vaccine responses. Haemodialysis patients over 60 years old will receive both Influenza and RSV vaccines plus either no additional treatment or a peri-vaccination regimen of sirolimus (rapamycin) to determine the most effective regimen to test further.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toby Coates, MBBS FRACP PhD; Phone Number: (08) 7074 0000; Email: Toby.Coates@sa.gov.au
• Study Contact Backup: Name: Griffith Perkins, BSc PhD; Email: Griffith.Perkins@adelaide.edu.au

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
      • Contact: Steve Chadban, MBBS PhD FRACP; Phone Number: (02) 9515 6111; Email: Steve.Chadban@health.nsw.gov.au
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
      • Contact: Matthew Tunbridge, MBBS FRACP; Phone Number: (07) 3176 2111; Email: Matthew.Tunbridge@health.qld.gov.au
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
      • Contact: Toby Coates, MBBS PhD FRACP; Phone Number: (08) 7074 0000; Email: Toby.Coates@sa.gov.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Influenza and RSV vaccination without additional treatment	Biological: Influenza vaccine (Sequiris Fluad Quad); All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad); Biological: RSV vaccine (Pfizer Abrysvo); All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo)
Experimental: Pre-vaccine sirolimus group; Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks after completing sirolimus course.	Biological: Influenza vaccine (Sequiris Fluad Quad); All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad); Biological: RSV vaccine (Pfizer Abrysvo); All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo); Drug: Sirolimus (RAPAMUNE); All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.; Other Names: Rapamycin
Experimental: Peri-vaccine sirolimus group; Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 1 week after commencing sirolimus course.	Biological: Influenza vaccine (Sequiris Fluad Quad); All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad); Biological: RSV vaccine (Pfizer Abrysvo); All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo); Drug: Sirolimus (RAPAMUNE); All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.; Other Names: Rapamycin
Experimental: Post-vaccine sirolimus group; Sirolimus 2mg orally x3/week on haemodialysis for 3 weeks. Influenza and RSV vaccination 2 weeks prior to commencing sirolimus course.	Biological: Influenza vaccine (Sequiris Fluad Quad); All participants will receive a dose of the seasonal Influenza vaccine (Sequiris Fluad Quad); Biological: RSV vaccine (Pfizer Abrysvo); All participants will receive a dose of the RSV vaccine (Pfizer Abrysvo); Drug: Sirolimus (RAPAMUNE); All treatment groups will receive 9 doses of 2mg sirolimus over a 3 week period, at varying times relative to vaccination.; Other Names: Rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine-specific functional T cell memory	The change in functional T cell memory from baseline to six weeks post vaccine dose, measured as IFN-γ spot-forming units (SFU) by ELISpot following 18-hour stimulation of PBMCs with RSV peptides.	Six weeks post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular immune response to vaccination	RSV vaccine-specific cellular immunity, measured as 1) change in frequency of CD8+ RSV F protein-specific T cells from baseline to six weeks post vaccine dose, identified by flow cytometry as CD8+CD134+CD69+ following 24-hour stimulation with a protein-derived peptide array (AIM, Activation-Induced Marker assay); 2) Change in frequency of RSV F protein-specific polyfunctional T cells from baseline to six weeks post vaccine dose. Polyfunctional T cells are defined as CD4+ T cells that produce more than one of IFN-γ, IL-2 and TNF identified by flow cytometry intracellular cytokine staining following 24-hour stimulation with a protein-derived peptide array (ICS, Intracellular Cytokine Staining assay).	Six weeks post vaccination
Vaccine-specific humoral immune response	Measures of vaccine-specific humoral immunity, measured as 1) Anti-RSV F protein IgM, IgA and IgG antibody titres 6 weeks following the vaccine dose; 2) Change in haemagglutination inhibition (HAI) titre of influenza strains contained in the 2026 vaccine from baseline to six weeks post vaccination.	Six week post vaccination
Incidence of infection post-vaccination	Incidence of RSV or Influenza infection in the study cohort from 3 weeks post vaccination to 12-month follow-up	Twelve months post vaccination
Incidence of Sirolimus (Rapamycin) Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety and tolerability of 3-week course of low-dose sirolimus (rapamycin), measured as frequency of adverse events (including serious adverse events)	Six week post vaccination
Incidence of Immunization Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety and tolerability of vaccine regimen, assessed by 1. Frequency of adverse events following immunization (AEFI), including adverse events of special interest (AESI) such as recurrence of autoimmune disease	Six weeks post vaccination
Quality of life questionnaire	Quality of life following 3-week course of low-dose sirolimus (rapamycin) and vaccination, measured with the EQ-5D-5L quality of life questionnaire. This questionnaire reports on 5 functional domains using an ordinal scale from 1 (worst) to 5 (best) to provide a combined health state score.	Six weeks post-vaccination
Circulating IL-1β analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-1β from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-α2 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IFN-α2 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IFN-γ analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IFN-γ from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating TNF-α analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors TNF-α from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating MCP-1 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors MCP-1 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-6 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-6 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CXCL8 (IL-8)	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor CXCL8 (IL-8) from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-10 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-10 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-12p70 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factor IL-12p70 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-17A analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-17A from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-18 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-18 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-23 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-23 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating IL-33 analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors IL-33 from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)
Circulating CRP analysis	Pre- and post-sirolimus circulating cytokine and chemokine analysis, measured as change in concentration of serum factors CRP from baseline to the end of sirolimus administration.	Three weeks after commencement of sirolimus (after administration of final dose of sirolimus)

Collaborators and Investigators

• Sponsor: Central Adelaide Local Health Network Incorporated

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: older adults; vaccine; influenza; RSV; immunosenescence; haemodialysis
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Organic Chemicals; Macrolides; Lactones; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Sirolimus; Influenza Vaccines; Respiratory Syncytial Virus Vaccines
• Other Study ID Numbers: 2025/HRE00483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized patient-level data created for the study will be available in a persistent repository upon publication. Data will be uploaded to figshare.com.
• IPD Sharing Time Frame: Anonymized IPD will be made available in a persistent repository from the date of publication of trial findings.
• IPD Sharing Access Criteria: Anonymized IPD will be publicly accessible by download from the persistent repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No