Herpes Zoster, Influenza
Conditions
Keywords
Vaccination, Trained immunity, Immunosenescence, Inflammaging
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
Interventions
BIOLOGICALHerpes zoster vaccination (Shingrix, GSK)
Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations
BIOLOGICALInfluenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)
Fluarix Tetra is a quadrivalent inactivated influenza vaccine
BIOLOGICALPlacebo
0.9% NaCl
Sponsors
GlaxoSmithKline
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cytokine productions of PBMCs upon incubation with viral, bacterial, and fungal antigens | 2 months after influenza vaccination | IL-6, TNF, IL-1b, IFNg cytokine concentrations will be measured. |
| Change in transcriptional profile of individual cells from PBMC population | 2 months after influenza vaccination | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. |
| Transcriptional profile of individual cells from PBMC population | 2 months after the first dose of herpes zoster vaccination | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the adaptive immune cell populations in blood | 2 months after influenza vaccination | Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS. |
| Baseline DNA methylation | Baseline (before vaccination) | CpG methylation profile of PBMCs |
| Changes in B and T cell receptor repertoires | 2 months after influenza vaccination | B and T cell receptors will be sequenced. |
| Changes in circulating protein concentrations | 2 months after influenza vaccination | Concentrations of circulating inflammatory proteins, including TNF, IL-6, IL-8, CCL3, CCL4, CXCL9, CXCL10, CXCL11, will be measured by Olink. |
| Shingles vaccine-specific antibody production in the serum | 2 months after the first herpes zoster vaccination | Anti-gE titers will be measured. |
| Percentage of participants reporting systemic events | 7 days after influenza and herpes zoster vaccination | Fever, fatigue, headache, chills, vomiting, diarrhea |
| Changes in epigenetic markers in PBMCs | 2 months after influenza vaccination | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. |
| C-reactive protein in the serum | Baseline (before vaccination) | Soluble C-reactive protein (CRP) concentrations will be measured. |
| Influenza vaccine-specific antibodies in the serum | 2 months after influenza vaccination | HAI titers will be measured. |
| Shingles vaccine-specific antibody production in serum | 2 months after the second herpes zoster vaccination | Anti-gE titers will be measured. |
| Percentage of participants reporting local reactions | 7 days after influenza and herpes zoster vaccination | Pain at the injection site, redness, and swelling |
Countries
Netherlands
Outcome results
None listed