Clinical trial NCT05082688: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Herpes Zoster
Keywords: Vaccination
Trained immunity
Immunosenescence
Inflammaging
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2021-10-19
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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

Primary outcomes:
measure: Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
timeFrame: 2 months after influenza vaccination
measure: Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
timeFrame: 6 months after influenza vaccination
measure: Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
timeFrame: 2 months after the first dose of herpes zoster vaccination
measure: Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
timeFrame: 2 months after the second dose of herpes zoster vaccination
measure: Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens
timeFrame: 6 months after the second dose of herpes zoster vaccination
measure: Change in transcriptional profile of individual cells from PBMC population
timeFrame: 2 months after influenza vaccination
measure: Change in transcriptional profile of individual cells from PBMC population
timeFrame: 6 months after influenza vaccination
measure: Transcriptional profile of individual cells from PBMC population
timeFrame: 2 months after the first dose of herpes zoster vaccination
measure: Transcriptional profile of individual cells from PBMC population
timeFrame: 2 months after the second dose of herpes zoster vaccination
measure: Transcriptional profile of individual cells from PBMC population
timeFrame: 6 months after the second dose of herpes zoster vaccination
Secondary outcomes:
measure: Changes in the adaptive immune cell populations in blood
timeFrame: 2 months after influenza vaccination
measure: Changes in the adaptive immune cell populations in blood
timeFrame: 6 months after influenza vaccination
measure: Changes in the adaptive immune cell populations in blood
timeFrame: 2 months after the first dose of herpes zoster vaccination
measure: Changes in the adaptive immune cell populations in blood
timeFrame: 2 months after the second dose of herpes zoster vaccination
measure: Changes in the adaptive immune cell populations in blood
timeFrame: 6 months after the second dose of herpes zoster vaccination
measure: Baseline DNA methylation
timeFrame: Baseline (before vaccination)
measure: Changes in B and T cell receptor repertoires
timeFrame: 2 months after influenza vaccination
measure: Changes in B and T cell receptor repertoires
timeFrame: 2 months after the first dose of herpes zoster vaccination
measure: Changes in B and T cell receptor repertoires
timeFrame: 2 months after the second dose of herpes zoster vaccination
measure: Changes in circulating protein concentrations
timeFrame: 2 months after influenza vaccination
measure: Changes in circulating protein concentrations
timeFrame: 2 months after the first dose of herpes zoster vaccination
measure: Changes in circulating protein concentrations
timeFrame: 2 months after the second dose of herpes zoster vaccination
measure: Influenza vaccine-specific antibodies in the serum
timeFrame: 2 months after influenza vaccination
measure: Shingles vaccine-specific antibody production in the serum
timeFrame: 2 months after the first herpes zoster vaccination
measure: Shingles vaccine-specific antibody production in serum
timeFrame: 2 months after the second herpes zoster vaccination
measure: Percentage of participants reporting local reactions
timeFrame: 7 days after influenza and herpes zoster vaccination
measure: Percentage of participants reporting systemic events
timeFrame: 7 days after influenza and herpes zoster vaccination
measure: Changes in epigenetic markers in PBMCs
timeFrame: 2 months after influenza vaccination
measure: Changes in epigenetic markers in PBMCs
timeFrame: 6 months after influenza vaccination
measure: Changes in epigenetic markers in PBMCs
timeFrame: 2 months after the first herpes zoster vaccination
measure: Changes in epigenetic markers in PBMCs
timeFrame: 2 months after the second herpes zoster vaccination
measure: Changes in epigenetic markers in PBMCs
timeFrame: 6 months after the second herpes zoster vaccination
measure: C-reactive protein in the serum
timeFrame: Baseline (before vaccination)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Jaap ten Oever, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: