Immunogenicity of Influenza Vaccinations

Measuring Immunity Against Circulating Influenza Viruses: Randomized Immunogenicity Study Among US Adults Aged 18-64 Years Comparing Two Approved Influenza Vaccines

This study is a randomized immunogenicity study in an enrolled cohort with active surveillance for influenza-like illness (ILI). During this study, participants will be randomly assigned to receive an approved cell culture-based influenza vaccine (Flucelvax) versus a licensed comparator influenza vaccine (Flublok or Fluzone). Blood samples from participants will be collected for measurement of biomarkers of immune response at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Participants will be asked if they wish to also provide saliva specimens at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Serum and peripheral blood mononuclear cells (PBMC) and plasma samples will be isolated from whole blood and tested for biomarkers of vaccine immunogenicity, and duration of antibody responses.

Participants will receive electronic surveys via email or text message weekly asking about changes in health status and new ILI symptoms; those reporting illness may be asked to provide a respiratory swab for laboratory testing for influenza and other respiratory viruses and up to 2 additional blood draws (acute [<10 days after symptom onset] and convalescent [28 days after acute visit if lab-confirmed positive for influenza]).

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Flucelvax (ccIIV4); Biological: Flublok (RIV) or Fluzone (IIV)

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Valleywise Health Comprehensive Health Center
    • Tempe, Arizona, United States, 85281
      • ASU Biodesign Institute
  • Georgia
    • Atlanta, Georgia, United States, 30333
      • Centers for Disease Control and Prevention
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University IDCRU
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44106
      • VA Northeast Ohio Healthcare System (VANEOHS)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Department of Family Medicine, University of Pittsburgh School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults aged 18-64 years that have not received the current season's influenza vaccine
2. English literate
3. Email or text message capability for weekly follow-up
4. Intention of receiving influenza vaccine based on ACIP-CDC guidelines
5. Willing to provide written/electronic informed consent
6. Intention of being available for entire study period and able to complete all relevant study procedures, including follow-up phone calls and clinic visits

Exclusion Criteria:

1. Receipt of the current season's influenza vaccine (receipt after July 1, 2024)
2. History of severe allergic reaction after a previous dose of any influenza vaccine or to an influenza vaccine component
3. Receipt of any licensed or investigational live vaccine within 6 weeks or non-live vaccine within 2 weeks prior to enrollment in this study or planning receipt of any vaccines between visits 1 and 2 of the study (approximately within 4 weeks after the receipt of study-administered vaccine)
4. History of Guillain-Barré syndrome
5. Currently pregnant, planning to become pregnant within the first three months of the study per participant self-report
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
7. Any condition which, in the opinion of the investigators, may pose a health risk to the participant or interfere with the evaluation of the study objectives

Temporary Delay Criteria (Visit 1)

1. History of febrile illness (> 100.0°F or 37.8°C) within the past 72 hours prior to vaccine administration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flucelvax (ccIIV4); Participants will receive Flucelvax (ccIIV4) at Visit 1.	Biological: Flucelvax (ccIIV4); Participants will receive Flucelvax (ccIIV4)
Experimental: Flublok (RIV) or Fluzone (IIV); Participants will receive Flublok (RIV) or Fluzone (IIV) at Visit 1.	Biological: Flublok (RIV) or Fluzone (IIV); Participants will receive Flublok (RIV) or Fluzone (IIV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with a seroprotective HAI titer (≥1:40)	The number (percent) of participants with a seroprotective HAI titer (≥1:40) for each influenza vaccine antigen	Baseline, Day 29
The geometric mean titer (GMT) of HAI antibody	The geometric mean titer (GMT) of HAI antibody for each influenza vaccine antigen	Baseline, Day 29
Number of participants demonstrating seroconversion from baseline	The number (percent) of participants in each vaccination group demonstrating seroconversion from Baseline at Day 29 (a titer ≥1:40 at Day 29 if the baseline titer is <1:10 or a four-fold rise in titer at Day 29 if the baseline titer is >1:10) as assessed by HAI titer for each vaccine antigen	Day 29
Geometric mean fold rise (GMFR) in HAI titer from baseline	The geometric mean fold rise (GMFR) in HAI titer from Baseline to Day 29 across HAI titers for each influenza vaccine antigen	Day 29

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Washington University School of Medicine; University of Pittsburgh; Centers for Disease Control and Prevention; University Hospitals Cleveland Medical Center; Arizona State University; VA Medical Center-Cleveland
• Investigators: Principal Investigator: Emmanuel B Walter, MD, MPH, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Actual): December 9, 2024
• Study Completion (Actual): June 4, 2025

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Immunogenicity
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: Pro00115120

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes