Systems Biology of Zoster Vaccine

Systems Biology of Zoster Vaccine Recombinant, Adjuvanted (SHINGRIX)

The purpose of the study is to better understand how the immune system responds to the new herpes zoster (shingles) vaccine (Shingrix®). The study will be looking at certain markers in the blood after vaccination with Shingrix®.

Study Overview

• Status: Completed
• Conditions: Zoster; Zoster Varicella; Shingles; Chicken Pox
• Intervention / Treatment: Biological: Shingrix®

Detailed Description

Varicella zoster virus (VZV) can cause two distinct diseases: chicken pox (varicella) and herpes zoster (shingles). The primary infection with VZV causes chicken pox, a widespread rash occurring with fever, mostly in childhood. The virus can then remain dormant in a person's body and has the ability to reactivate later in life causing shingles. Shingles is a painful rash, occurring mostly in older individuals or those who have a weakened immune system. After resolution of the rash, individuals may experience persistent pain in the same area, called post-herpetic neuralgia.

The purpose of the study is to better understand how the immune system responds to the new herpes zoster (shingles) vaccine (Shingrix®). In particular, looking at certain markers in the blood after vaccination with Shingrix®.

The study will be an open label clinical trial in healthy older adults. There will be two groups of participants: those aged 50 to 60 years or those who are 70 years old and above, both groups will receive the vaccine. This will help compare the immune response to the herpes zoster vaccine in different age cohorts of older adults.

Subjects will be recruited by flyer advertisements. Interested individuals will be screened for the study and if they qualify they will be consented and enrolled in the study. Blood samples will be collected and banked. There are optional storage of data/specimens for future research including: being contacted for future studies, having contact information and limited medical information entered into a clinic database, and storage of Protected Health Information and samples for future research (yes, no, and de-identified).

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30030
      • The Hope Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subject must be able to understand and provide informed consent.
2. Adults aged 50-60 years, or community dwelling adults aged 70 years and above.

Exclusion Criteria:

1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol.

2. Receipt of immune products:

   • Receipt of blood products within 6 months prior of the first dose of the study Zoster vaccine or expected receipt through 6 months after vaccination with the second dose of the study Zoster vaccine.
   • Receipt of any vaccine within 4 weeks prior to vaccination with any of the two doses of the study Zoster vaccine or expected receipt within 4 weeks after vaccination with any of the two doses of the study Zoster vaccine.
   • Receipt of any Zoster or varicella vaccines at any time prior to study entry.
3. Subject taking any non-topical antiviral therapy with activity against herpes viruses, including but not limited to acyclovir, famciclovir, valacyclovir, and ganciclovir 3 days prior to each vaccination or 14 days after.
4. Prior history of shingles.

5. Presence of certain co morbidities or immunosuppressive states such as:

   • Chronic medical problems including (but not limited to) insulin-dependent diabetes, severe (at the discretion of the investigator or study physician) heart, lung, liver, or kidney diseases; auto immune diseases; severe gastrointestinal diseases; and uncontrolled hypertension.
   • Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C, tuberculosis, organ transplant, cancer, current and or expected receipt of chemotherapy, radiation therapy, steroids [i.e., > 20 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 90 days); (nasal (less than 1mg/day of fluticasone equivalent inhaled corticosteroid is allowable) and topical steroids are allowed)], antitumor necrosis factor agents, or any other immunosuppressive therapy, anatomic or functional asplenia, congenital immunodeficiency.

6. Conditions that could affect the safety of the subjects such as:

   • Severe reactions to prior vaccinations.
   • History of anaphylactic/anaphylactoid reaction to any component of the vaccines.
   • History of bleeding disorders.
7. Any acute illness, including any fever (> 100.4 F [> 38.0 C], regardless of the route) within 3 days prior to study entry.
8. Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.
9. Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data.
10. Use of investigational drugs within 12 months of participation.
11. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator or study physician, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
12. Women of childbearing potential.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Younger Group; Participants between the ages of 50 to 60 years will receive two doses of Zoster vaccine recombinant, adjuvanted (Shingrix®)	Biological: Shingrix®; A zoster vaccine recombinant, adjuvanted, recently approved by the FDA for prevention of herpes zoster (shingles) in adults aged 50 years and older. It is given in two doses (0.5 mL each): at 0 and 2 to 6 months.
Experimental: Older Group; Participants who are ≥70 year old will receive two doses of Zoster vaccine recombinant, adjuvanted (Shingrix®)	Biological: Shingrix®; A zoster vaccine recombinant, adjuvanted, recently approved by the FDA for prevention of herpes zoster (shingles) in adults aged 50 years and older. It is given in two doses (0.5 mL each): at 0 and 2 to 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Innate Immune Signatures Post-vaccine Dose	Will be assessed between D0, D1, and D7 and each dose of Zoster vaccine recombinant, adjuvanted, in both age cohorts: 50-60 years and >70 years of age. Results will be reported using Mean Normalized Enrichment Score (NES) of the Antiviral Interferon Signature Module (NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the score (less activity), and a positive score reflects more activity of the module).	Day 1 from Day 0, Day 7 from Day 0, Day 61 from day 60, Day 67 from day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Zoster Vaccine Recombinant, Adjuvanted	Differences in related adverse events and serious adverse events between each dose of Zoster vaccine recombinant, adjuvanted, in both age cohorts. Number of participants with related AEs and SAEs (assessed within 7 days post-vaccination) will be reported.	Day 270 post-intervention

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Nadine Rouphael, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2019
• Primary Completion (Actual): April 3, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Vaccine; Shingles; Zoster; Clinical Trials; Immune responses; Vaccine Trials; Chicken Pox
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster; Chickenpox
• Other Study ID Numbers: IRB00105838; 1U19AI090023 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: At the time of publication or 9 months after submission of the manuscript. It will be available indefinitely.

IPD Sharing Access Criteria

Data will be uploaded into www.immport.org and made available to researchers with a registered account.

Type of Analysis: Any Purpose

Mode of Access: Data will be shared on www.immport.org

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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