Safety and Immunogenicity of Non-live, Recombinant Subunit Herpes Zoster Vaccine Before and After Lung Transplantation

The investigators plan to study the immunogenicity of the vaccine before and after lung transplantation. Patients (at least 50 years old) before and after lung transplantation will be enrolled. The investigators hypothesize that the recombinant varicella-zoster subunit vaccine is able to induce cellular immunogenicity after transplantation.

Study Overview

• Status: Unknown
• Conditions: Varicella Zoster Vaccine
• Intervention / Treatment: Biological: VZV subunit vaccine

Detailed Description

Solid organ transplant recipients receive lifelong immunosuppression and are at increased risk for reactivation of all herpesviruses including VZV. Epidemiologic studies show the cumulative incidence in lung transplant recipients of reactivation to be 15-20%. A non-live, recombinant subunit vaccine (Shingrix; GSK vaccines) was recently licensed for the prevention of shingles in people aged 50 years or older. The investigators plan to study the immunogenicity of the vaccine before and after lung transplantation. Patients (at least 50 years old) before and after lung transplantation will be enrolled. The investigators hypothesize that the recombinant varicella-zoster subunit vaccine is able to induce cellular immunogenicity after transplantation.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2N2
      • University Health Network, Toronto General Hospital, Multi-Organ Transplant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria Post-Transplant Vaccine Group:

• Single or double lung transplant recipient.
• Age ≥50 years

Exclusion Criteria Post-Transplant Vaccine Group:

• Has already received varicella zoster subunit vaccine in the past
• Shingles within the last 12 months
• Ongoing CMV viremia > 200 IU/mL
• HIV infection
• Diagnosis of malignancy (eg PTLD)

Inclusion Criteria Pre-Transplant Vaccine Group:

• On waiting list for lung transplantation
• Age ≥50 years

Exclusion Criteria Pre-Transplant Vaccine Group:

• Has already received Shingrix or Zostavax (live shingles vaccine) in the past
• Systemic prednisone ≥20 mg per day (or equivalent dose of any corticosteroid)
• Other (than prednisone < 20mg per day or equivalent dose of any corticosteroid) systemic immunosuppressive therapy such as mycophenolate or tacrolimus
• Shingles within the last 12 months
• HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pre-Transplant Group; VZV Subunit vaccine will be administered	Biological: VZV subunit vaccine; VZV subunit vaccine
Experimental: Post-Transplant Group; VZV Subunit vaccine will be administered	Biological: VZV subunit vaccine; VZV subunit vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular immunity to varicella zoster induced by varicella zoster subunit vaccine.	Cellular immunogenicity against VZV induced by varicella zoster subunit vaccine in lung transplant recipients measured as a percentage of CD4+ and CD8+ T-cells measured by intracellular flow-cytometry based staining. The cellular immunogenicity of the vaccine in lung transplant recipients will be compared to the control group (pre-transplant vaccination).	4 weeks after second dose of vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral immunogenicity to varicella zoster induced by varicella zoster subunit vaccine in lung transplant recipients.	Humoral immunogenicity (increase of GMTs of anti-VZV antibodies) in lung transplant	4 weeks after second dose of vaccine
Humoral immunogenicity to varicella zoster induced by varicella zoster subunit vaccine in post-transplant group vs. pre-transplant group	Humoral immunogenicity (GMTs of anti-VZV antibodies compared pre and post vaccination) against VZV induced by varicella zoster subunit vaccine in lung transplant recipients compared to the pre-transplant control group.	4 weeks after second dose of vaccine

Collaborators and Investigators

• Sponsor: Deepali Kumar
• Investigators: Principal Investigator: Deepali Kumar, MD, Multi organ transplant program, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): September 5, 2019
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: UHN-Shingrix-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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