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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-005682-13 | EudraCT Number |
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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1: Young adults herpes zoster vaccination | Experimental | Young adults between 18 and 35 years old will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose. |
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| 2: Older adults herpes zoster vaccination | Experimental | Adults older than 60 years of age will receive the herpes zoster vaccine (Shingrix). 60 days later, they will receive a booster dose. |
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| 3: Young adults influenza vaccination | Experimental | Young adults between 18 and 35 years old will receive the influenza vaccine (Fluarix Tetra). |
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| 4: Older adults influenza vaccination | Experimental | Adults older than 60 years of age will receive the influenza vaccine (Fluarix Tetra). |
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| 5: Young adults herpes zoster vaccination related placebo | Placebo Comparator | Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl). 60 days later, they will receive another placebo. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Herpes zoster vaccination (Shingrix, GSK) | Biological | Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 months after influenza vaccination |
| 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. | 6 months after influenza vaccination |
| 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. | 2 months after the first dose of herpes zoster vaccination |
| 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. | 2 months after the second dose of herpes zoster vaccination |
| 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. | 6 months after the second dose of herpes zoster vaccination |
| Change in transcriptional profile of individual cells from PBMC population | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. | 2 months after influenza vaccination |
| Change in transcriptional profile of individual cells from PBMC population |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 months after influenza vaccination |
| Changes in the adaptive immune cell populations in blood |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jaap ten Oever, MD, PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University | Nijmegen | Gelderland | 6525GA | Netherlands |
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| 6: Young adults influenza vaccination related placebo | Placebo Comparator | Young adults between 18 and 35 years old will receive the placebo injection (0.9% NaCl). |
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| Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK) | Biological | Fluarix Tetra is a quadrivalent inactivated influenza vaccine |
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| Placebo | Biological | 0.9% NaCl |
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Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. |
| 6 months after influenza vaccination |
| Transcriptional profile of individual cells from PBMC population | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. | 2 months after the first dose of herpes zoster vaccination |
| Transcriptional profile of individual cells from PBMC population | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. | 2 months after the second dose of herpes zoster vaccination |
| Transcriptional profile of individual cells from PBMC population | Gene expression profile of PBMCs will be measured by single cell-RNA sequencing. | 6 months after the second dose of herpes zoster vaccination |
Ratio of adaptive immune cells (T and B cells) and their subtypes will be measured by FACS.
| 6 months after influenza vaccination |
| 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. | 2 months after the first dose of herpes zoster vaccination |
| 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. | 2 months after the second dose of herpes zoster vaccination |
| 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. | 6 months after the second dose of herpes zoster vaccination |
| Baseline DNA methylation | CpG methylation profile of PBMCs | Baseline (before vaccination) |
| Changes in B and T cell receptor repertoires | B and T cell receptors will be sequenced. | 2 months after influenza vaccination |
| Changes in B and T cell receptor repertoires | B and T cell receptors will be sequenced. | 2 months after the first dose of herpes zoster vaccination |
| Changes in B and T cell receptor repertoires | B and T cell receptors will be sequenced. | 2 months after the second dose of herpes zoster vaccination |
| 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. | 2 months after influenza vaccination |
| 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. | 2 months after the first dose of herpes zoster vaccination |
| 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. | 2 months after the second dose of herpes zoster vaccination |
| Influenza vaccine-specific antibodies in the serum | HAI titers will be measured. | 2 months after influenza vaccination |
| Shingles vaccine-specific antibody production in the serum | Anti-gE titers will be measured. | 2 months after the first herpes zoster vaccination |
| Shingles vaccine-specific antibody production in serum | Anti-gE titers will be measured. | 2 months after the second herpes zoster vaccination |
| Percentage of participants reporting local reactions | Pain at the injection site, redness, and swelling | 7 days after influenza and herpes zoster vaccination |
| Percentage of participants reporting systemic events | Fever, fatigue, headache, chills, vomiting, diarrhea | 7 days after influenza and herpes zoster vaccination |
| Changes in epigenetic markers in PBMCs | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. | 2 months after influenza vaccination |
| Changes in epigenetic markers in PBMCs | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. | 6 months after influenza vaccination |
| Changes in epigenetic markers in PBMCs | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. | 2 months after the first herpes zoster vaccination |
| Changes in epigenetic markers in PBMCs | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. | 2 months after the second herpes zoster vaccination |
| Changes in epigenetic markers in PBMCs | ATAC-sequencing will be performed to measure post transcriptional modifications (methylation, acetylation, etc) on histones. | 6 months after the second herpes zoster vaccination |
| C-reactive protein in the serum | Soluble C-reactive protein (CRP) concentrations will be measured. | Baseline (before vaccination) |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| D006562 | Herpes Zoster |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D000073618 | Varicella Zoster Virus Infection |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
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| ID | Term |
|---|---|
| C023768 | halofantrine |
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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