The goal of this clinical trial is to measure the immune response in the blood, nose, and lungs after participants receive either the FDA-approved inactivated influenza vaccine or the FDA-approved intranasal FluMist vaccine. The study will evaluate immune responses in groups of healthy, non-pregnant, volunteers between the ages of 18 and 40. The main purpose of the study is to measure the change in influenza vaccine-specific antibodies in the lower lungs and nose between vaccination and 14 days after participants receive the vaccine. All participants will be randomized to receive one of the two seasonal flu vaccines and will have blood and back of the nose swabs collected throughout the study. Some study participants will choose to undergo optional bronchoscopy procedures and will be included in the part of the study looking at lower lung immune responses.
Study Design/Methodology: Prospective randomized controlled trial; Study Duration: 2 years; Number of Subjects: 30; Subject Participation Duration: 4 months; Description of Interventions: Eligible healthy participants who have not received a seasonal influenza vaccine within the past 9 months will complete written informed consent. Enrolled participants will be randomized to receive either an FDA-approved intramuscular seasonal egg-based inactivated influenza vaccine (IIV) (N=15) or the FDA-approved seasonal FluMist intranasal live attenuated influenza vaccine (N=15) on study day 0. Blood samples and nasopharyngeal swabs will be collected at the time of study enrollment (up to 45 days prior to vaccination) and on days 3±1, 7±2, 14±3, 28±5, and 90±14 post-vaccination. Sixteen participants (N=8 in each vaccine group) will be enrolled for optional research bronchoscopy procedures. Research bronchoscopies will include bronchoalveolar lavage (BAL) and endobronchial biopsy (EBBx) sample collection. Research bronchoscopies will be performed prior to vaccination and on study days 14±3 and 90±14. Screening safety laboratory studies and screening chest x-ray imaging will be performed on subjects undergoing research bronchoscopies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
30
intranasal administered live attenuated influenza vaccine
intramuscular administered inactivated influenza vaccine
bronchoscopy with bronchoalveolar lavage and endobronchial biopsy sampling
Washington University in Saint Louis School of Medicine Emergency Care and Research Core
St Louis, Missouri, United States
RECRUITINGChange in vaccine-specific mucosal antibody response following vaccination
Measure the change in influenza vaccine strain-specific hemagglutinin and neuraminidase antibody titers found at the upper and lower airway mucosal surface between day 0 and day 14 after administration of FluMist intranasal influenza vaccination versus standard dose trivalent IIV using ELISA.
Time frame: From samples before vaccination and day 14 after vaccination.
Change in vaccine-specific circulating antibody following vaccination.
Measure the change in influenza vaccine strain-specific antibody titers found in blood between day 0 and day 14 after administration of FluMist intranasal influenza vaccination versus standard dose IIV using ELISA.
Time frame: From samples before vaccination and day 14 after vaccination.
Change in influenza-specific mucosal and circulating CD8+ T cells following vaccination.
Measure the change in the magnitude of influenza-specific CD8+ T cells found in the blood, the nasopharynx, the lower airways and the lung tissue between day 0 and day 14 using flow cytometry with influenza-specific HLA class I tetramer reagents.
Time frame: From samples before vaccination and day 14 after vaccination.
Change in influenza-specific mucosal and circulating B cells following vaccination.
Measure the change in the magnitude of influenza-specific B cells found in the blood and the lung tissue between day 0 and day 14 using flow cytometry with influenza strain-specific fluorescently-labeled HA probes.
Time frame: From samples before vaccination and day 14 after vaccination.
Change in vaccine-specific mucosal antibody response 3 months after vaccination
Measure the change in influenza vaccine strain-specific antibody titers found at the lower airway mucosal surface and at the nasopharyngeal mucosal surface between day 14 and day 90 using ELISA.
Time frame: From samples taken on day 14 after vaccination and day 90 after vaccination.
Change in influenza-specific mucosal and circulating CD8+ T cells and B cells 3 months after vaccination.
Measure the change in the magnitude of influenza-specific CD8+ T cells and B cells found in the blood, the nasopharynx, the lower airways and the lung tissue between day 14 and day 90 using flow cytometry with influenza-specific HLA class I tetramer reagents and strain-specific fluorescently-labeled HA probes.
Time frame: From samples taken on day 14 after vaccination and day 90 after vaccination.
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