Effect of High-Dose Quadrivalent Influenza Vaccine (Efluelda®) Versus Standard-Dose (QIV-SD), in Subjects 65 Years of Age and Older on Innate Immunity, Including Gene Expression (INFLUOMICS)

The purpose of the study is to evaluate innate and adaptive immunity following QIV-HD vaccination compared to QIV-SD vaccination in people 65 years of age and older.

Study Overview

• Status: Completed
• Conditions: Vaccine Reaction
• Intervention / Treatment: Biological: Experimental arm : High-Dose Quadrivalent Influenza Vaccine (Efluelda); Biological: Active Comparator: Standard-Dose Quadrivalent Influenza Vaccine

Detailed Description

The hypothesis is that higher dose of antigen can increase the intensity and the quality of innate immunity, as the adaptive humoral and cellular responses.

In this study, the objectif is to evaluate innate and adaptive immunity following QIV-HD vaccination compared to QIV-SD vaccination in people 65 years of age and older.

Modifications of early blood molecular (transcriptome) and cellular (blood phenotyping) signatures within the first 24 hours following vaccination will be investigated. The association between early gene signature and late influenza-specific humoral immune responses weeks/months after vaccination will be also assessed.

This study is a hase IV, randomized, open-label, active-controlled, multi-center study comparing the immune response induced by QIV-HD vaccine (intervention) and QIV-SD vaccine (control).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Annecy, France, 74370
    • Centre Hospitalier Annecy Genevois
  • Chambéry, France
    • Centre Hospitalier Metropole Savoie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 65 years or older, the day of inclusion;
2. Have signed and dated Informed Consent Form;
3. Able and willing to attend all scheduled visits, and to comply with study procedures;
4. Covered by French health insurance.

Non-Inclusion Criteria :

1. Any vaccine injection (including COVID-19 vaccine) in the 4 weeks preceding study inclusion;
2. Plan to receive any vaccine (including COVID-19 vaccine) in the 4 weeks following study inclusion;
3. Already vaccinated against influenza for 2021-2022 season;
4. Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances;
5. HIV infection;
6. Active Hepatitis B, or active Hepatitis C;
7. Previous Guillain Barré syndrome;
8. Ongoing immunosuppressive treatment or active immunodeficiency;
9. Receipt of immune globulins, blood or blood-derived products in the past 3 months;
10. Thrombocytopenia or bleeding disorder, receipt of anticoagulants contraindicating IM vaccination based on investigator's judgment;
11. Influenza-like illness symptoms, including COVID-19, within 4 weeks before study inclusion;
12. Personnes referred to in articles L1121-6 and L1121-8 of Public Health Code (persons deprived of liberty by judicial or administrative decision and persons subject to a legal protection measure: guardianship or curatorship).

Exclusion Criteria:

1. Any subject presenting with influenza-like illness symptoms, including COVID-19 between inclusion (visit 1) and randomization (visit 2);
2. Subject unable to attempt visit at Day 0 (visit 2) and Day 1 (visit 3);
3. Blood sample at Day 0 (visit 2) impossible to obtain;
4. Receipt of vaccine injection or equivalent between inclusion (visit 1) and randomization (visit 2), other than those allowed and planned in the study. This includes non-study dose of 2021-2022 influenza vaccine, blood-derived immune globulins, blood, or blood-derived products.
5. Any unexpected event relevant to the physician in charge, after discussion with the coordinating investigator and the sponsor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Dose Quadrivalent Influenza Vaccine; One injection of the high-dose Efluelda vaccine will be given to the patient	Biological: Experimental arm : High-Dose Quadrivalent Influenza Vaccine (Efluelda); Patient will received one dose of High Dose Quadrivalent Influenza Vaccine according to marketing authorization.
Active Comparator: Standard-Dose Quadrivalent Influenza Vaccine; One injection of the standard-dose Influvactetra vaccine will be given to the patient	Biological: Active Comparator: Standard-Dose Quadrivalent Influenza Vaccine; Patient will received one dose of Standard Dose Quadrivalent Influenza Vaccine according to marketing authorization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Transcriptomic profiles	Transcriptomic profiles of blood cells (microarrays) will be performed to measure early systemic innate immune response	Change from Baseline Transcriptomic profiles at day after vaccine injection (Day 1)
Change of Innate cellular phenotyping	Innate cellular phenotyping will be performed using 36 surface markers deciphering lineage cells monocytes, neutrophils, NK, antigen-presenting cells.	Change from Baseline Innate cellular phenotyping at day after vaccine injection (Day 1)
Change of Gene signature	Study of the transcriptional profile of the blood cells by microarrays	Change from Baseline Gene signature at day after vaccine injection (Day 1)
Humoral immune responses	HAI titers, Individual HAI titers ratio, Subjects with titers ≥ 40, Seroconversion	Day 0, Day 21, Day 90 and Day 210 time

Collaborators and Investigators

• Sponsor: Centre Hospitalier Annecy Genevois
• Collaborators: Hospices Civils de Lyon; Institut National de la Santé Et de la Recherche Médicale, France; Sanofi Pasteur, a Sanofi Company; Eurofins Optimed; Euraxi Pharma
• Investigators: Principal Investigator: Cecile JANSSEN, Ch Annecy Genevois

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): July 21, 2022
• Study Completion (Actual): July 21, 2022

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Actual): August 8, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 21-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No