The purpose of this study is to evaluate the immune response produced by a seasonal live attenuated influenza vaccine (LAIV) when compared to placebo. The initial vaccination will be followed 2 months later by an inpatient trial evaluating safety, infectivity, clinical response, and viral shedding after exposure to the wild-type A/California/2009-like influenza challenge virus.
This study will evaluate the immune response produced by a seasonal LAIV. The initial vaccination will be followed 2 months later by an open-label inpatient trial evaluating the subsequent response (safety, infectivity, clinical response, and viral shedding) following administration of the wild-type A/California/2009-like influenza challenge virus. Healthy adult participants will be randomized into two groups. On Day 0, Group 1 will receive a single dose of an intranasal LAIV. Group 2 will receive a single dose of intranasal placebo. Study visits will occur on Days 0, 3, 7, 14, and 28. On Day 54, participants will be admitted to the isolation unit for the inpatient portion of the study, and both groups will receive an intranasal dose of wild-type A/California/2009-like influenza challenge virus on Day 56. On Day 65, participants who are no longer shedding virus will be discharged. Follow-up study visits will occur after discharge from the isolation unit on Days 70, 84, 112, and 180. Study visits during either the inpatient or outpatient portions of the trial may include physical examinations, collection of blood and urine samples, electrocardiogram (ECG), nasal washes and swabs, and nasal mucus weighing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
10\^7.0 fluorescent focus units (FFU); administered by intranasal spray
Administered by intranasal spray
Approximately 3.5 x 10\^6 TCID50; administered intranasally
University of Rochester Medical Center
Rochester, New York, United States
Frequency of any reactogenicity events after administration of seasonal LAIV
Time frame: Measured through Day 180
Frequency of significant increases in nasal secretion hemagglutination (HA)-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)
Time frame: Measured through Day 84
Frequency of instances of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immuno spot assay (ELISPOT)
Time frame: Measured on Day 28 after immunization
Frequency of detection of influenza-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) secreting B cells assessed by antibody secreting cells (ASC) assay
Time frame: Measured on Day 7 following vaccination
Frequency of challenge virus shedding on one or more days on Days 56-63 as assessed by culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR)
Time frame: Measured through Day 63
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by HAI assays
Time frame: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by MN assays
Time frame: Measured through Day 56
A 4-fold or greater increase in either hemagglutination-inhibition (HAI) or microneutralization (MN) antibody when compared to pre-challenge samples, as assessed by blood serum titer
Time frame: Measured through Day 56
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Clinical symptoms recording of 10 key influenza symptoms (cough, sore throat, stuffy nose, dyspnea, fatigue, headache, myalgias, nausea, diarrhea, and feverishness) on an analog scale of severity
Time frame: Measured through Day 180
Area under the curve (AUC) of symptom severity
Time frame: Measured through Day 180
Total nasal mucus weight
Nasal mucus weights will be determined by collecting tissues over 24 hours, weighing them and subtracting the dry weight.
Time frame: Measured through Day 180