Clinical trial NCT05518500: A Deep Longitudinal Analysis of Next Generation Influenza Vaccines in Older Adults
Official title: A Deep Longitudinal Analysis of Next Generation Influenza Vaccines in Older Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Aging
Influenza Vaccine
Dendritic Cell
Vaccine Response
Lead sponsor: The Jackson Laboratory
Sponsor class: OTHER
Collaborators: name: UConn Health
name: Icahn School of Medicine at Mount Sinai
name: Weill Medical College of Cornell University
name: University of Chicago
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-08-26
Enrollment: 75
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this study.

Detailed description: This prospective, single-arm study is designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults through the establishment of the FluVax3 cohort of healthy older adults. In this study, the investigators will perform comprehensive profiling of blood antibodies and immune cells over time, and associate specific age-related immune alterations with vaccine responder or non-responder status. This will allow the investigators to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help the investigators progress towards developing a universal influenza vaccine. The results are expected to provide the foundation for new approaches to improve overall vaccine efficacy and protection in older adults, an outcome of significant public health relevance considering the vulnerability of this population.

In this study, up to seventy-five (75) healthy adults aged 65 years and older who have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 flu season, FLUAD® Quadrivalent during the 2023-24 flu season and Flublok Quadrivalent in the 2024-2025 flu season. The study sample will be drawn from the population of healthy older participants in the catchment area of UConn Health in Farmington, CT.

Study participation will involve six study visits around the flu vaccine each year and one final study visit for a total of nineteen study visits over three years. Blood samples will be collected at sixteen study visits for transcriptional, epigenetic and biological analyses pre- and post-vaccination. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. These microbiome samples will be stored and used in future research. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study.

This project will yield an unparalleled dataset from healthy older adults that will be used to identify fundamental mechanisms, cell populations, and pathways associated with durable protective antibody immune responses, and lack thereof, upon influenza vaccination. In sum, this study will reveal the mechanistic alterations that explain the heterogeneity in response to vaccines observed in older individuals. Understanding this heterogeneity opens the possibility of stratifying older adults for personalized vaccines. In addition, understanding the mechanistic overlap between the correlates of responsiveness to three different influenza vaccines will advance the ultimate development of a universal influenza vaccine, which is a key focus of NIAID's influenza research program. Finally, this study will generate a considerable amount of transcriptional and functional data related to the outputs of key innate immune and T/B-cell subsets involved in responses to influenza vaccines in older adults. These data will collectively become an important resource for future studies focused on the older adult immune system in health and disease.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
  * Severe autoimmune disease requiring biological therapy
  * Diabetes mellitus requiring insulin
  * Use of medicines during past 6 months known to alter immune response such as high-dose corticosteroids (≥ 10 mg/day of prednisone or equivalent)
  * HIV, AIDS or other immunodeficiency disorders
  * Recent (≤ 3 months) severe trauma or major surgery (PI to evaluate)
  * Current substance and/or alcohol abuse
* Patients currently residing in the Department of Correction
* Inability to comply with the protocol requirements
* Any other condition that, in the opinion of the PI, might interfere with study objectives

Primary outcomes:
measure: Change in Antibody Responses to Influenza Vaccine Year One
timeFrame: Baseline, Day 35, Day 180
measure: Change in Antibody Responses to Influenza Vaccine Year Two
timeFrame: Baseline, Day 35, Day 180
measure: Change in Antibody Responses to Influenza Vaccine Year Three
timeFrame: Baseline, Day 35, Day 180
Secondary outcomes:
measure: Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year One
timeFrame: Baseline, Day 7, Day 35
measure: Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year Two
timeFrame: Baseline, Day 7, Day 35
measure: Evaluate changes in functional status of immune cells in response to Influenza Vaccine in Year Three
timeFrame: Baseline, Day 7, Day 35
measure: Number of genes upregulated in response to Influenza Vaccine in Year One
timeFrame: Baseline, Day1, Day 7
measure: Number of genes upregulated in response to Influenza Vaccine in Year Two
timeFrame: Baseline, Day 1, Day 7
measure: Number of genes upregulated in response to Influenza Vaccine in Year Three
timeFrame: Baseline, Day1, Day 7
measure: Number of chromatin accessibility regions activated in response to Influenza Vaccine in Year One
timeFrame: Baseline, Day1, Day 7
measure: Number of chromatin accessibility regions activated in response to Influenza Vaccine in Year Two
timeFrame: Baseline, Day1, Day 7
measure: Number of chromatin accessibility regions activated in response to Influenza Vaccine in Year Three
timeFrame: Baseline, Day1, Day 7
measure: Changes in number of cDCs, Tfh, Th10, and B lymphocytes in response to Influenza Vaccine in Year One
timeFrame: Baseline, Day1, Day 7, Day 35, Day 180
measure: Changes in number of cDCs, Tfh, Th10, and B lymphocytes in response to Influenza Vaccine in Year Two
timeFrame: Baseline, Day1, Day 7, Day 35, Day 180
measure: Changes in number of cDCs, Tfh, Th10, and B lymphocytes in response to Influenza Vaccine in Year Three
timeFrame: Baseline, Day1, Day 7, Day 35, Day 180
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UConn Health, Center On Aging
state: Connecticut
Study officials:
affiliation: UConn Center on Aging
name: George Kuchel, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References: