Healthy, Influenza
Conditions
Keywords
Inactivated influenza vaccine quadrivalent, Live, attenuated influenza vaccine quadrivalent, Monozygotic twins, Dizygotic twins, Adults, Adolescents
Brief summary
The purpose of the study is to investigate and compare the immune responses to influenza vaccination in monozygotic (identical) and dizygotic (fraternal) twins to determine the roles of genetics and environment in the response to flu vaccination.
Detailed description
This is a phase 1 study of 120 healthy 12-49 year old adolescents and adult volunteers who are given licensed seasonal influenza vaccine. There are no exclusions for gender, ethnicity or race. The volunteers will be enrolled into one of 3 groups: Group A: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+ 7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group B: Up to 40 healthy dizygotic (DZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). Group C: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be randomized within the twin pair to receive either inactivated influenza vaccine quadrivalent (IIV4) or live, attenuated influenza vaccine quadrivalent (LAIV4). Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). This group was terminated in 2016 due to ACIP recommendations against the use of LAIV but was reopened in 2018 with the availability of LAIV4. Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs.
Interventions
BIOLOGICALFluMist® Quadrivalent
LAIV4 vaccine dosage is 0.2 mL. Vaccine will be administered as an intranasal spray. Each sprayer contains a single dose of FluMist® Quadrivalent; approximately one-half of the contents should be administered into each nostril. 0.1 mL (i.e., half of the dose from a single FluMist sprayer) is administered into each nostril while the recipient is in an upright position. Insert the tip of the sprayer just inside the nose and rapidly depress the plunger until the dose-divider clip stops the plunger. The dose divider clip is removed from the sprayer to administer the second half of the dose (0.1 mL) into the other nostril.
BIOLOGICALFluzone® Quadrivalent vaccine
IIV4 vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Otherwise healthy, 12-49 years old, identical (MZ) or fraternal (DZ) twins. 2. Willing to complete the informed consent process (including assent for minors 12-17 years of age, inclusive). 3. Availability for follow-up for the planned duration of the study at least 28 days after immunization. 4. Acceptable medical history by review of inclusion/
Exclusion criteria
and vital signs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hemagglutination inhibition (HAI) titers in response to influenza vaccination. | Day 0 to Day 28 |
| Interferon-gamma (IFN-γ) production by T cells | Day 0 to Day 28 |
| IFN-γ production by Natural Killer (NK) cells. | Day 0 to Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sequencing of T-cell receptor (TCR)ab and Immunoglobulin Genes | Day 0 to Day 28 | B and T cells will be sequenced for their antibody repertoires. |
| Natural Killer (NK) repertoire. | Day 0 to Day 28 | Mass cytometry will be used to assess the NK cell repertoire. |
Countries
United States
Outcome results
None listed