Immunologic Response to FluMist vs. Flucelvax

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate immunologic response to different types of influenza vaccine among children/adolescents/young adults 4-21 years of age. This is a randomized controlled trial (RCT), that will assess immune response in about 440 participants (about 220 per vaccine arm) pre- and post-vaccination to FluMist (live attenuated influenza vaccine given by nasal administration) and Flucelvax (egg-free cell-culture inactivated influenza vaccine).

Detailed Description
-----------------
This is a non-blinded, randomized controlled trial analyzing influenza vaccine immunogenicity response in children/adolescents/young adults aged 4-21 years given one of two FDA approved and licensed influenza vaccines: FluMist (live attenuated influenza vaccine by nasal administration) and Flucelvax (egg-free cell-culture inactivated influenza vaccine). This study will enroll about 440 healthy participants, about 220 per vaccine arm. Participants will be randomized in blocks of 4 using a 1:1 allocation to receive either FluMist or Flucelvax. Blood work will be conducted on all participants at baseline prior to vaccine receipt and post-vaccination at Day 7 (range 6-9 days) and Day 28 (range 21-35 days). The primary objective of the study is to determine pre- and post-serologic responses to each vaccine type.

Official Title
-----------------
Immunological Response to Influenza Vaccination in Children, Adolescents, and Young Adults: A RCT of FluMist vs. Flucelvax

Conditions
-----------------
Influenza, Human, Immune Response

Intervention / Treatment
-----------------
* Biological: FluMist live attenuated influenza vaccine
* Biological: Flucelvax inactivated influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: aged 4-21 years; has prior vaccination history available (which can be determined based either on medical record review or through state registry review); plans to receive the current seasonal influenza vaccination at one of the recruiting sites Exclusion Criteria: unable or unwilling to completed required study activities, including informed consent, randomization to vaccine, and bloodwork; has already received influenza vaccine for the current season; has a known immunocompromising condition or is on an immunosuppressing medication (e.g., high dose steroids >10 days); is known to be pregnant; has a history of severe allergy to eggs or to influenza vaccine or any of its components

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FluMist live attenuated influenza vaccine<br>Participants receiving live attenuated FluMist influenza vaccine will receive 0.2 mL given intranasally | Biological: FluMist live attenuated influenza vaccine<br>* Participants randomized to this study influenza vaccine arm will receive FluMist live attenuated influenza vaccine at baseline after the baseline blood draw is complete.<br>|
| Active Comparator: Flucelvax inactivated influenza vaccine<br>Participants receiving inactivated Flucelvax influenza vaccine will receive 0.5 mL given intramuscularly | Biological: Flucelvax inactivated influenza vaccine<br>* Participants randomized to this study influenza vaccine arm will receive Flucelvax cell-culture inactivated influenza vaccine at baseline after the baseline blood draw is complete.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroconversion Response In 2019 | Rows in data tables represent different influenza antigens measured in 2019. Hemagglutination inhibition (HI) assay was conducted to assess immunologic outcome. Seroconversion is defined as a 4-fold or higher rise in HI titer post-vaccination given a pre-vaccination HI titer of >=10 and a final HI titer of >=40. | Post-vaccination (at Day 28 timepoint) | 
| Number of Participants With Seroconversion Response In 2020 | Rows in data tables represent different influenza antigens measured in 2020. Hemagglutination inhibition (HI) assay was conducted to assess immunologic outcome. Seroconversion is defined as a 4-fold or higher rise in HI titer post-vaccination given a pre-vaccination HI titer of >=10 and a final HI titer of >=40. | Post-vaccination (at Day 28 timepoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Seroprotection Response in 2019 | Rows in data tables represent different influenza antigens measured in 2019. Hemagglutination inhibition (HI) assay was conducted to assess immunologic outcome. Seroprotection is defined as a HI titer >= 1:110 at either time point. | Pre-vaccination (at Day 0 timepoint) and post-vaccination (at Day 28 timepoint) | 
| Geometric Mean Titers (GMTs) at Each Time Point 2019 | Rows in data tables represent different influenza antigens measured in 2019. Hemagglutination inhibition assay was conducted to assess immunologic outcome. GMTs is defined as the anti-log of the mean of the log2 HI titers | Pre-vaccination (at Day 0 timepoint) and post-vaccination (at Day 28 timepoint) | 
| Number of Participants With Seroprotection Response in 2020 | Rows in data tables represent different influenza antigens measured in 2020. Hemagglutination inhibition (HI) assay was conducted to assess immunologic outcome. Seroprotection is defined as a HI titer >= 1:110 at either time point. | Pre-vaccination (at Day 0 timepoint) and post-vaccination (at Day 28 timepoint) | 
| Geometric Mean Titers (GMTs) at Each Time Point 2020 | Rows in data tables represent different influenza antigens measured in 2020. Hemagglutination inhibition assay will be conducted to assess immunologic outcome. GMTs is defined as the anti-log of the mean of the log2 HI titers | Pre-vaccination (at Day 0 timepoint) and post-vaccination (at Day 28 timepoint) |