Age Differences in Influenza & Herpes Zoster Vaccine NCT05082688

Clinical Trial Details — Status: Completed

Administrative data
NCT number	NCT05082688
Other study ID #	NL76061.091.20
Secondary ID	2020-005682-13
Status	Completed
Phase	Phase 2
First received
Last updated
Start date	September 20, 2021
Est. completion date	May 17, 2023

Study information
Verified date	June 2023
Source	Radboud University Medical Center
Contact	n/a
Is FDA regulated	No
Health authority
Study type	Interventional

Clinical Trial 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.

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

Recruitment information / eligibility
Status	Completed
Enrollment	148
Est. completion date	May 17, 2023
Est. primary completion date	May 17, 2023
Accepts healthy volunteers	Accepts Healthy Volunteers
Gender	All
Age group	18 Years and older
Eligibility	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

Study Design

Related Conditions & MeSH terms

Intervention

Biological:
• Herpes zoster vaccination (Shingrix, GSK)
Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations
• Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)
Fluarix Tetra is a quadrivalent inactivated influenza vaccine
• Placebo
0.9% NaCl

Locations
Country	Name	City	State
Netherlands	Radboud University	Nijmegen	Gelderland

Sponsors *(2)*
Lead Sponsor	Collaborator
Radboud University Medical Center	GlaxoSmithKline

Country where clinical trial is conducted

Netherlands,

Outcome
Type	Measure	Description	Time frame
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Change in transcriptional profile of individual cells from PBMC population	Gene expression profile of PBMCs will be measured by single cell-RNA sequencing.	6 months after influenza vaccination
Primary	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
Primary	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
Primary	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
Secondary	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
Secondary	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 influenza vaccination
Secondary	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
Secondary	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
Secondary	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
Secondary	Baseline DNA methylation	CpG methylation profile of PBMCs	Baseline (before vaccination)
Secondary	Changes in B and T cell receptor repertoires	B and T cell receptors will be sequenced.	2 months after influenza vaccination
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Influenza vaccine-specific antibodies in the serum	HAI titers will be measured.	2 months after influenza vaccination
Secondary	Shingles vaccine-specific antibody production in the serum	Anti-gE titers will be measured.	2 months after the first herpes zoster vaccination
Secondary	Shingles vaccine-specific antibody production in serum	Anti-gE titers will be measured.	2 months after the second herpes zoster vaccination
Secondary	Percentage of participants reporting local reactions	Pain at the injection site, redness, and swelling	7 days after influenza and herpes zoster vaccination
Secondary	Percentage of participants reporting systemic events	Fever, fatigue, headache, chills, vomiting, diarrhea	7 days after influenza and herpes zoster vaccination
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	C-reactive protein in the serum	Soluble C-reactive protein (CRP) concentrations will be measured.	Baseline (before vaccination)

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

Clinical Trial Details — Status: Completed

Administrative data

Study information

Clinical Trial Summary

Description:

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Intervention

Locations

Sponsors (2)

Country where clinical trial is conducted

Outcome