A Deep Longitudinal Analysis of Next Generation Influenza Vaccines in Older Adults

NCT05518500 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: 22-179J-1U01AI165452
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm study designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults. The investigators will recruit and longitudinally follow a cohort of 75 older adults (65 years and older) who will receive three different influenza vaccines over three annual influenza seasons. Blood samples will be collected from the participants at sixteen study visits over three years. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. After completion of study visits other than the End of Study visit around vaccination in Year 3, participants will be offered the opportunity to be vaccinated with a different FDA approved influenza vaccine and participate in study visits for Year 4. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this study.

Conditions

Aging; Influenza Vaccine; Dendritic Cell; Vaccine Response

Outcome Measures

Primary Outcomes (4)

• Change in Antibody Responses to Influenza Vaccine Year One

  In year one, healthy older participants will receive Fluzone Quadrivalent HD vaccine. Longitudinal blood samples will be collected and influenza-specific antibody responses will be assessed. Change in antibody response will be measured using Hemagglutination Inhibition (HAI) from baseline to day 35 and day 180.

  Baseline, Day 35, Day 180

• Change in Antibody Responses to Influenza Vaccine Year Two

  In year two, healthy older participants will receive FLUAD vaccine. Longitudinal blood samples will be collected and influenza-specific antibody responses will be assessed. Change in antibody response will be measured using Hemagglutination Inhibition (HAI) from baseline to day 35 and day 180.

  Baseline, Day 35, Day 180

• Change in Antibody Responses to Influenza Vaccine Year Three

  In year three, healthy older participants will receive Flublok Quadrivalent vaccine. Longitudinal blood samples will be collected and influenza-specific antibody responses will be assessed. Change in antibody response will be measured using Hemagglutination Inhibition (HAI) from baseline to day 35 and day 180.

  Baseline, Day 35, Day 180

• Change in Antibody Responses to Influenza Vaccine Year Four

  In year four, healthy older participants will receive Fluzone® High-Dose Trivalent vaccine. Longitudinal blood samples will be collected and influenza-specific antibody responses will be assessed. Change in antibody response will be measured using Hemagglutination Inhibition (HAI) from baseline to day 35 and day 180.

  Baseline, Day 35, Day 180

Secondary Outcomes (16)

• Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year One

  Baseline, Day 7, Day 35

• Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year Two

  Baseline, Day 7, Day 35

• Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year Three

  Baseline, Day 7, Day 35

• Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year Four

  Baseline, Day 7, Day 35

• Number of genes upregulated in response to Influenza Vaccine in Year One

  Baseline, Day1, Day 7

Study Arms (1)

Healthy Older Adults

EXPERIMENTAL

Will receive FDA-approved influenza vaccine (Fluzone HD (Quadrivalent) Year 1, FLUAD Year 2, Flublok Quadrivalent Year 3, Fluzone HD (Trivalent) Year 4)

Biological: Flu Vaccine (Year 1); Biological: Flu Vaccine (Year 2); Biological: Flu Vaccine (Year 3); Biological: Flu Vaccine (Year 4)

Interventions

Flu Vaccine (Year 1) BIOLOGICAL

Participants will receive Fluzone® Quadrivalent High-Dose in the 2022-2023 flu season.

Also known as: Fluzone® Quadrivalent High-Dose

Healthy Older Adults

Flu Vaccine (Year 2) BIOLOGICAL

Participants will receive FLUAD® Quadrivalent in the 2023-2024 flu season.

Also known as: FLUAD

Healthy Older Adults

Flu Vaccine (Year 3) BIOLOGICAL

Participants will receive Flublok Quadrivalent in the 2024-2025 flu season.

Also known as: Flublok Quadrivalent

Healthy Older Adults

Flu Vaccine (Year 4) BIOLOGICAL

Participants will receive Fluzone® High-Dose Trivalent in the 2025-2026 flu season.

Also known as: Fluzone® High-Dose Trivalent

Healthy Older Adults

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Able to speak and read English
• Male or Female, 65 years and older by date of enrollment
• Weight of 110 lbs or greater
• Has received influenza vaccine in the past seasons without severe adverse reactions
• Willing to receive an FDA-approved age-appropriate and CDC-recommended influenza vaccine for each of the 2022-23, 2023-24, and 2024-25 influenza seasons
• Willing to withhold all other vaccinations 2 weeks prior and 2 weeks after flu vaccination for the 2022-23, 2023-24, and 2024-25 influenza seasons
• Willing and available to participate in 19 study visits over three years around influenza vaccination
• Willing to provide blood samples at sixteen visits over three years
• Willing to agree to genomic testing of samples and sharing of de-identified genomic data generated from samples at the conclusion of the research

You may not qualify if:

• Received any vaccine (shingles, pneumococcal, COVID, etc.) within 2 weeks of anticipated flu vaccination for the 2022-23, 2023-24, and 2024-25 influenza seasons.
• Has already received an influenza vaccine for the approaching influenza season (2022-23)
• Has known allergy to eggs or any component of the flu vaccine. \[Although the Advisory Committee on Immunization Practices (ACIP) has concluded that a history of anaphylactic/anaphylactoid or severe allergic reaction to eggs should no longer be considered a contraindication to vaccination with any age-appropriate vaccine, for the purposes of this research study we elected to exclude individuals with these allergies\]
• History of Guillain-Barre syndrome (GBS)
• Body temperature greater than 100.3°F (38°C) on date of vaccination or within 2 days prior to vaccination by participant report (study entry may be delayed to meet this requirement)
• Rockwood Frailty Index score of \>0.21
• Known history of any of the following co-morbid conditions:
• Chronic or recent (within past 2 months) infection requiring oral or intravenous antibiotics, antifungals, or antivirals
• Cancer other than basal cell carcinoma requiring active surgical or medical treatment (chemotherapy or radiation therapy)
• Congestive Heart Failure
• Ischemic Heart Disease
• Congenital abnormalities (PI to evaluate)
• Paget's disease
• Renal failure requiring ongoing dialysis
• Chronic obstructive pulmonary disease, emphysema, or asthma

Sponsors & Collaborators

• Weill Medical College of Cornell University: collaborator
• University of Chicago: collaborator
• The Jackson Laboratory: lead
• UConn Health: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

UConn Health, Center On Aging

Farmington, Connecticut, 06030, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• George Kuchel, MD, FRCP

  UConn Center on Aging

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 2, 2022
• First Posted: August 26, 2022
• Study Start: August 31, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Conclusion of the study
• Access Criteria: Pending dbGaP/ImmPORT registration

Locations

US (1)