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Age Differences in Influenza and Herpes Zoster Vaccine Responses (INFLUENZA-SHINGRIX)

Primary Purpose

Influenza, Herpes Zoster

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Herpes zoster vaccination (Shingrix, GSK)
Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)
Placebo
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Influenza focused on measuring Vaccination, Trained immunity, Immunosenescence, Inflammaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age between 18-35 years old OR age ≥60 years old
  • Written informed consent

Exclusion Criteria:

  • Known allergy to (components of) the influenza or herpes zoster vaccine
  • Immunocompromised subjects and subjects with active malignancy within the last two years
  • Previous herpes zoster vaccination in the last year
  • Receipt of any vaccination 4 weeks prior to the start of the study or plans to receive any other vaccination in the first 2 months after inclusion
  • Use of systemic immunomodulatory drugs:steroids, anti-inflammatory biological treatments (e.g. anti-cytokine monoclonal antibodies)
  • Acute or active illness within two weeks prior to the start of the study
  • Pregnant, breastfeeding or planning to become pregnant during the study period

Sites / Locations

  • Radboud University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

1: Young adults herpes zoster vaccination

2: Older adults herpes zoster vaccination

3: Young adults influenza vaccination

4: Older adults influenza vaccination

5: Young adults herpes zoster vaccination related placebo

6: Young adults influenza vaccination related placebo

Arm Description

Young adults between 18 and 35 years old will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.

Adults older than 60 years of age will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.

Young adults between 18 and 35 years old will receive the influenza vaccine (Fluarix Tetra).

Adults older than 60 years of age will receive the influenza vaccine (Fluarix Tetra).

Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl). 60 days later, they will receive another placebo.

Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl).

Outcomes

Primary Outcome Measures

Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Change in transcriptional profile of individual cells from PBMC population
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Change in transcriptional profile of individual cells from PBMC population
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Transcriptional profile of individual cells from PBMC population
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.

Secondary Outcome Measures

Changes in the adaptive immune cell populations in blood
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Changes in the adaptive immune cell populations in blood
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Changes in the adaptive immune cell populations in blood
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Changes in the adaptive immune cell populations in blood
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Changes in the adaptive immune cell populations in blood
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Baseline DNA methylation
CpG methylation profile of PBMCs
Changes in B and T cell receptor repertoires
B and T cell receptors will be sequenced.
Changes in B and T cell receptor repertoires
B and T cell receptors will be sequenced.
Changes in B and T cell receptor repertoires
B and T cell receptors will be sequenced.
Changes in circulating protein concentrations
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Changes in circulating protein concentrations
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Changes in circulating protein concentrations
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Influenza vaccine-specific antibodies in the serum
HAI titers will be measured.
Shingles vaccine-specific antibody production in the serum
Anti-gE titers will be measured.
Shingles vaccine-specific antibody production in serum
Anti-gE titers will be measured.
Percentage of participants reporting local reactions
Pain at the injection site, redness, and swelling
Percentage of participants reporting systemic events
Fever, fatigue, headache, chills, vomiting, diarrhea
Changes in epigenetic markers in PBMCs
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Changes in epigenetic markers in PBMCs
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Changes in epigenetic markers in PBMCs
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Changes in epigenetic markers in PBMCs
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Changes in epigenetic markers in PBMCs
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
C-reactive protein in the serum
Soluble C-reactive protein (CRP) concentrations will be measured.

Full Information

First Posted
January 22, 2021
Last Updated
June 28, 2023
Sponsor
Radboud University Medical Center
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05082688
Brief Title
Age Differences in Influenza and Herpes Zoster Vaccine Responses (INFLUENZA-SHINGRIX)
Official Title
Exploratory Study Into Age-related Immunological Differences Related to Immunogenicity in Influenza Vaccination and Herpes Zoster Vaccination
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 20, 2021 (Actual)
Primary Completion Date
May 17, 2023 (Actual)
Study Completion Date
May 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Vaccines are used to prevent infectious diseases worldwide. Unfortunately, many vaccines, like the flu vaccine, are less effective in older adults. This single-centre open label partially randomised, partially placebo-controlled trial evaluates the differences in immune response between young and older adults after vaccination with a quadrivalent inactivated influenza vaccine and an adjuvanted herpes zoster vaccination. Exploring the underlying mechanisms between the differences in immunogenicity can provide important information for future vaccine development.
Detailed Description
Rationale: Vaccination of the older adults is often advised as they are a high-risk population; however, vaccine efficacy generally decreases with age. This is mainly due to a decrease in adaptive immune responses known as immunosenescence, which is a factor influencing the response to influenza vaccination. On the other hand, there are vaccines that show high efficacy (more than 95%) in older adults, one of the most effective being the AS01 adjuvanted herpes zoster vaccine, Shingrix. The differential immune pathways associated with vaccine responsiveness as well as the immune mechanisms by which adjuvants overcome immunosenescence remain poorly understood. Targeting key immune pathways could be a way to improve vaccine efficacy in older adults. Objective: To explore immunological features between young and older adults after administration of an adjuvanted herpes zoster (Shingrix) or influenza unadjuvanted (Fluarix) vaccine that could explain differences in vaccine immunogenicity. Study design: A single centre open label, randomised, and partially placebo-controlled trial Study population: Approximately 140 healthy adults, 80 of which are between 18-35 years old, the other 60 are 60+ years old. Intervention: Two groups of young and elderly volunteers receive recombinant zoster vaccine (Shingrix), while two other groups will receive a quadrivalent influenza vaccine (Fluarix). Two groups of young volunteers will receive a placebo. Main study parameter: To identify immune senescence-related differences contributing to vaccine immunogenicity

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Herpes Zoster
Keywords
Vaccination, Trained immunity, Immunosenescence, Inflammaging

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
148 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1: Young adults herpes zoster vaccination
Arm Type
Experimental
Arm Description
Young adults between 18 and 35 years old will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.
Arm Title
2: Older adults herpes zoster vaccination
Arm Type
Experimental
Arm Description
Adults older than 60 years of age will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose.
Arm Title
3: Young adults influenza vaccination
Arm Type
Experimental
Arm Description
Young adults between 18 and 35 years old will receive the influenza vaccine (Fluarix Tetra).
Arm Title
4: Older adults influenza vaccination
Arm Type
Experimental
Arm Description
Adults older than 60 years of age will receive the influenza vaccine (Fluarix Tetra).
Arm Title
5: Young adults herpes zoster vaccination related placebo
Arm Type
Placebo Comparator
Arm Description
Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl). 60 days later, they will receive another placebo.
Arm Title
6: Young adults influenza vaccination related placebo
Arm Type
Placebo Comparator
Arm Description
Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl).
Intervention Type
Biological
Intervention Name(s)
Herpes zoster vaccination (Shingrix, GSK)
Intervention Description
Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations
Intervention Type
Biological
Intervention Name(s)
Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)
Intervention Description
Fluarix Tetra is a quadrivalent inactivated influenza vaccine
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
0.9% NaCl
Primary Outcome Measure Information:
Title
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
Description
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Time Frame
2 months after influenza vaccination
Title
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
Description
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Time Frame
6 months after influenza vaccination
Title
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
Description
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Time Frame
2 months after the first dose of herpes zoster vaccination
Title
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
Description
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Time Frame
2 months after the second dose of herpes zoster vaccination
Title
Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
Description
IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured.
Time Frame
6 months after the second dose of herpes zoster vaccination
Title
Change in transcriptional profile of individual cells from PBMC population
Description
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Time Frame
2 months after influenza vaccination
Title
Change in transcriptional profile of individual cells from PBMC population
Description
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Time Frame
6 months after influenza vaccination
Title
Transcriptional profile of individual cells from PBMC population
Description
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Time Frame
2 months after the first dose of herpes zoster vaccination
Title
Transcriptional profile of individual cells from PBMC population
Description
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Time Frame
2 months after the second dose of herpes zoster vaccination
Title
Transcriptional profile of individual cells from PBMC population
Description
Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.
Time Frame
6 months after the second dose of herpes zoster vaccination
Secondary Outcome Measure Information:
Title
Changes in the adaptive immune cell populations in blood
Description
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Time Frame
2 months after influenza vaccination
Title
Changes in the adaptive immune cell populations in blood
Description
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Time Frame
6 months after influenza vaccination
Title
Changes in the adaptive immune cell populations in blood
Description
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Time Frame
2 months after the first dose of herpes zoster vaccination
Title
Changes in the adaptive immune cell populations in blood
Description
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Time Frame
2 months after the second dose of herpes zoster vaccination
Title
Changes in the adaptive immune cell populations in blood
Description
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
Time Frame
6 months after the second dose of herpes zoster vaccination
Title
Baseline DNA methylation
Description
CpG methylation profile of PBMCs
Time Frame
Baseline (before vaccination)
Title
Changes in B and T cell receptor repertoires
Description
B and T cell receptors will be sequenced.
Time Frame
2 months after influenza vaccination
Title
Changes in B and T cell receptor repertoires
Description
B and T cell receptors will be sequenced.
Time Frame
2 months after the first dose of herpes zoster vaccination
Title
Changes in B and T cell receptor repertoires
Description
B and T cell receptors will be sequenced.
Time Frame
2 months after the second dose of herpes zoster vaccination
Title
Changes in circulating protein concentrations
Description
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Time Frame
2 months after influenza vaccination
Title
Changes in circulating protein concentrations
Description
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Time Frame
2 months after the first dose of herpes zoster vaccination
Title
Changes in circulating protein concentrations
Description
Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink.
Time Frame
2 months after the second dose of herpes zoster vaccination
Title
Influenza vaccine-specific antibodies in the serum
Description
HAI titers will be measured.
Time Frame
2 months after influenza vaccination
Title
Shingles vaccine-specific antibody production in the serum
Description
Anti-gE titers will be measured.
Time Frame
2 months after the first herpes zoster vaccination
Title
Shingles vaccine-specific antibody production in serum
Description
Anti-gE titers will be measured.
Time Frame
2 months after the second herpes zoster vaccination
Title
Percentage of participants reporting local reactions
Description
Pain at the injection site, redness, and swelling
Time Frame
7 days after influenza and herpes zoster vaccination
Title
Percentage of participants reporting systemic events
Description
Fever, fatigue, headache, chills, vomiting, diarrhea
Time Frame
7 days after influenza and herpes zoster vaccination
Title
Changes in epigenetic markers in PBMCs
Description
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Time Frame
2 months after influenza vaccination
Title
Changes in epigenetic markers in PBMCs
Description
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Time Frame
6 months after influenza vaccination
Title
Changes in epigenetic markers in PBMCs
Description
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Time Frame
2 months after the first herpes zoster vaccination
Title
Changes in epigenetic markers in PBMCs
Description
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Time Frame
2 months after the second herpes zoster vaccination
Title
Changes in epigenetic markers in PBMCs
Description
ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones.
Time Frame
6 months after the second herpes zoster vaccination
Title
C-reactive protein in the serum
Description
Soluble C-reactive protein (CRP) concentrations will be measured.
Time Frame
Baseline (before vaccination)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age between 18-35 years old OR age ≥60 years old Written informed consent Exclusion Criteria: Known allergy to (components of) the influenza or herpes zoster vaccine Immunocompromised subjects and subjects with active malignancy within the last two years Previous herpes zoster vaccination in the last year Receipt of any vaccination 4 weeks prior to the start of the study or plans to receive any other vaccination in the first 2 months after inclusion Use of systemic immunomodulatory drugs:steroids, anti-inflammatory biological treatments (e.g. anti-cytokine monoclonal antibodies) Acute or active illness within two weeks prior to the start of the study Pregnant, breastfeeding or planning to become pregnant during the study period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaap ten Oever, MD, PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525GA
Country
Netherlands

12. IPD Sharing Statement

Learn more about this trial

Age Differences in Influenza and Herpes Zoster Vaccine Responses (INFLUENZA-SHINGRIX)

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