Recombinant Subunit Herpes Zoster Vaccine in VZV-Seronegative Organ Transplant Recipients

Safety and Immunogenicity of Non-live, Recombinant Subunit Herpes Zoster Vaccine in VZV-seronegative Solid Organ Transplant Recipients

The investigators plan to study the immunogenicity of the vaccine in VZV-seronegative solid organ transplant recipients. VZV-seronegative patients will be enrolled after organ transplantation. The investigators hypothesize that the recombinant subunit Herpes zoster vaccine is able to induce cellular immunogenicity after transplantation in VZV-seronegative patients.

Study Overview

• Status: Completed
• Conditions: Varicella Zoster Vaccine
• Intervention / Treatment: Biological: recombinant subunit Herpes zoster vaccine

Detailed Description

Solid organ transplant recipients receive lifelong immunosuppression and are at increased risk for severe primary VZV infection (chickenpox) and VZV reactivation (shingles). A non-live, recombinant subunit Herpes zoster vaccine (Shingrix; GSK vaccines) was recently licensed for the prevention of shingles in people aged 50 years or older and was shown to induce both cellular and humoral immunity. As both components of the immune system are important for protection against VZV, the investigators plan to study the humoral and cellular immunogenicity of the vaccine after organ transplantation in VZV-seronegative patients. Indeed, the current live VZV vaccine is contraindicated after transplantation; therefore, the non-live recombinant varicella-zoster subunit vaccine, if shown to induce cellular and humoral immunity, could potentially be offered to VZV-seronegative transplant patients.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

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

Description

Inclusion Criteria:

• Solid organ transplant recipient.
• Age ≥18 years
• VZV-seronegative at time of transplant
• ≥90 days post-transplant
• Able to provide informed consent

Exclusion Criteria:

• Has already received the recombinant subunit Herpes zoster vaccine in the past
• Ongoing CMV viremia > 200 IU/mL
• HIV infection
• Diagnosis of malignancy (e.g. PTLD)
• History of a severe allergic reaction (anaphylactic reaction) after any vaccine
• Documented Chickenpox or Shingles after transplantation
• Congenital immunodeficiency (e.g., CVID)
• Treatment for rejection in the past 30 days
• Immunoglobulin in the past 30 days or anticipated to receive immunoglobulin
• Anti-CD20 monoclonal antibody in the past 6 months or anticipated to receive Anti-CD20 monoclonal antibody
• Plasmapheresis in the past 30 days or anticipated to receive plasmapheresis
• Febrile illness in the past one week
• Unable to comply with the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VZV seronegative Transplant Patients; recombinant subunit Herpes zoster vaccine	Biological: recombinant subunit Herpes zoster vaccine; Seronegative Solid Organ Transplant patients will receive two doses of the subunit Herpes zoster vaccine at 0 and 2-6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral immunity to varicella zoster induced by the recombinant subunit Herpes zoster vaccine.	Fold increase in concentration of anti-gE antibody titer from pre- to post-vaccination	4 weeks after second dose of vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Vaccine-related Adverse Events	Adverse events will be graded as mild, moderate, severe	Up to 4 weeks after second dose of vaccine

Collaborators and Investigators

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

Publications and helpful links

General Publications

• L'Huillier AG, Hirzel C, Ferreira VH, Ierullo M, Ku T, Selzner N, Schiff J, Juvet S, Miao C, Schmid DS, Humar A, Kumar D. Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients. Transplantation. 2021 Oct 1;105(10):2316-2323. doi: 10.1097/TP.0000000000003621.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): September 5, 2019

Study Registration Dates

• First Submitted: September 23, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 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: UHNTID007

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