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

NCT ID: NCT05082688

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-20
• Study Completion Date: 2023-05-17

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

Conditions

Influenza; Herpes Zoster

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

1: Young adults herpes zoster vaccination

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

Group Type: EXPERIMENTAL

Herpes zoster vaccination (Shingrix, GSK)

Intervention Type: BIOLOGICAL

Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations

2: Older adults herpes zoster vaccination

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

Group Type: EXPERIMENTAL

Herpes zoster vaccination (Shingrix, GSK)

Intervention Type: BIOLOGICAL

Shingrix is an ASO1-adjuvanted herpes zoster vaccination used to prevent shingles and its associated complications in at-risk populations

3: Young adults influenza vaccination

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

Group Type: EXPERIMENTAL

Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)

Intervention Type: BIOLOGICAL

Fluarix Tetra is a quadrivalent inactivated influenza vaccine

4: Older adults influenza vaccination

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

Group Type: EXPERIMENTAL

Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)

Intervention Type: BIOLOGICAL

Fluarix Tetra is a quadrivalent inactivated influenza vaccine

5: Young adults herpes zoster vaccination related placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

0.9% NaCl

6: Young adults influenza vaccination related placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

0.9% NaCl

Interventions

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

Intervention Type: BIOLOGICAL

Influenza Vaccine (Fluarix Tetra Northern Hemisphere 2021 or 2022, GSK)

Fluarix Tetra is a quadrivalent inactivated influenza vaccine

Intervention Type: BIOLOGICAL

Placebo

0.9% NaCl

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaap ten Oever, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

2020-005682-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL76061.091.20

Identifier Type: -

Identifier Source: org_study_id