Systems Analyses of the Immune Response to the Seasonal Influenza Vaccine

Phase 2

Completed

• Conditions: Healthy Volunteer
• Interventions: Biological: Flucelvax; Biological: Fluvirin; Biological: Fluzone High Dose

• Registration Number: NCT04025580
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Background:

Vaccines help prevent disease by causing the body to have an immune response. Many parts of this response happen in the blood. This response happens over days and weeks after getting the vaccine. Researchers want to how the blood changes over time in response to vaccines. They want to find out why vaccines work better for some people than for others. This could help make more effective vaccines.

Objective:

To learn about how the body responds to vaccines.

Eligibility:

Healthy people ages 18 and older

Design:

Participants will be screened with a medical history, physical exam, and blood and urine tests.

Participants will have 9 visits over 6 months. All visits will include blood tests and a physical exam.

Participants will have the first visit 1 week before they get the vaccine.

Participants will get the flu vaccine at the second visit. The vaccine will be injected into the muscle of the upper arm with a needle. They will be watched for side effects for 15 minutes.

Participants will have the next 2 visits exactly 1 day and 1 week after they get the vaccine. They will have the other 5 visits about 14, 28, 70, and 100 days after they get the vaccine.

Participants will take email questionnaires about whether they had any side effects.

Participants may have optional extra study visits. These will be no more than once a month for up to 1 year after they get the vaccine. Optionally, they can also repeat the study each year through the 2023 - 2024 flu season

Detailed Description

Certain functions of the immune system are revealed only when the immune system is challenged. When a person is vaccinated, a coordinated response results: activation and interaction of distinct innate and adaptive immune cell populations and pathways, culminating in the formation of germinal centers from which antibody-producing plasma cells and memory B cells derive. By taking measurements at various time points before and after vaccination, we can build a comprehensive picture of how the immune system responds to a vaccine challenge.

The seasonal influenza vaccination provides an excellent model of coordinated immune activity involving innate and adaptive responses, as demonstrated in a past NIH study in 2009-2011; however, scientific advances and the possibility of multi-season responses in individuals warrant a new follow-up study with more comprehensive sampling. This is an open-label, prospective, exploratory study to assess the baseline and post-vaccination immune responses of healthy volunteers to an approved seasonal influenza vaccine. Subjects will undergo baseline blood collections on day -7 and on day 0 before receiving the study vaccine. After vaccination, blood will be collected on days 1, 7, 14, 28, 70, and 100. Optionally, subjects may also give blood once a month, as requested, up until 1 year after vaccination. Blood samples will be used to assess short- and long-term immunological effects of immunization. Evaluations will include vaccine antibody titers. Additional evaluations may include peripheral immune cell phenotyping, RNA sequencing (RNA-seq) of whole blood and defined peripheral blood cell subsets, and measurement of serum proteins and antibodies. Subjects may optionally provide stool samples at some visits for exploratory microbiome assessment. Additionally, subjects may optionally continue study participation annually through the 2023-24 influenza season.

The goal of this protocol is to use the collective information gathered across all healthy volunteers to understand how the immune system works as a whole.

Study Timeline

• Study First Submitted: 2019-07-18
• Study First Submitted QC: 2019-07-18
• Study First Posted: 2019-07-19
• Study Start: 2019-10-02
• Status Verified: 2023-01-31
• Primary Completion: 2023-01-31
• Study Completion: 2023-01-31
• Results First Submitted: 2023-10-03
• Results First Submitted QC: 2023-12-11
• Last Update Submitted: 2023-12-11
• Results First Posted: 2024-01-02
• Last Update Posted: 2024-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Flucelvax, Fluvirin, or Fluzone High Dose	Fluvirin	Healthy Volunteer between ages 18-65 receiving Flucelvax
Flucelvax, Fluvirin, or Fluzone High Dose	Fluzone High Dose	Healthy Volunteer between ages 18-65 receiving Flucelvax
Flucelvax, Fluvirin, or Fluzone High Dose	Flucelvax	Healthy Volunteer between ages 18-65 receiving Flucelvax

Primary Outcome Measures

Name	Time	Method
Microneutralization Titers	Day 0 and Day 28 Reported in Manuscript	Change in antibody titer response to vaccination, as measured by microneutralization titers at day 0 and day 70 and its relationship with novel baseline biomarkers

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States