PET-CT Scans in Healthy Volunteers After Flu Vaccination

Study Overview
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Brief Summary
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This study is being done to learn how previous flu vaccination or previous infection with flu virus affects the immune response to vaccination.

Detailed Description
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Until recently, all recipients of influenza vaccine received a killed form of virus, typically in the same nondominant arm, each year before flu season. We hypothesize that natural infection, and some forms of vaccination, could allow vaccine induced responses to spread beyond the local lymph nodes near the vaccination site. From a practical perspective, if vaccine induced proliferation of specific immune cells in sites distant from the vaccination site lead to beneficial immune memory, it would suggest vaccination strategies that could be as simple as alternating the injected arm from year to year, or alternating inhaled vs. injected forms of vaccine. This will be a 4 armed prospective study of individuals receiving unilateral FluShield i.m. Healthy adult volunteers 21-55 will be grouped according to the following criteria: I. Documented history of prior natural infection with influenza A or B within the past 5 years (diagnostic test or high titer hemagglutinin HA Ab in absence of vaccination); II. History of FluMist vaccination within the past 2 years; III. History of TIV (Trivalent (Inactivated) Influenza Vaccine) vaccination, any number of times, but only in a single (e.g., non-dominant) arm. Within one month of screening and baseline blood draws for PBMCs (Peripheral blood mononuclear cells) and Ab (antibody) titers, individuals will receive FluShield injections. For those individuals with prior history of unilateral TIV injections, half will receive their shots in the same arm that has always been injected (Group IIIa). The other half of these individuals will receive Flushield in the opposite (dominant) arm (Group IIIb). Upon entering the study, 50cc of heparinized blood and 10 cc of serum will be drawn by antecubital venipuncture. Within 4 weeks of this blood draw, volunteers will receive a standard dose of i.m. TIV (FluShield). Four-seven days later they will have an FDG PET-CT scan performed after an 8 hour fast. Additional blood draws of 50cc heparinized blood and 10 cc serum will be obtained at 2, 4, and 6 weeks post vaccination, and at 10-12 months post vaccination. After the last blood draw, volunteers will also be asked questions pertaining to flu-like symptoms during the past 10 months.

Official Title
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Impact of Bilateral Priming on Response to Unilateral Flu Vaccination

Conditions
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Flu

Intervention / Treatment
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* Biological: FluShield
* Biological: FluShield - same arm
* Biological: FluShield - opposite arm
* Procedure: Blood Draws
* Procedure: FDG PET-CT Scan
* Genetic: Cytokine Profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 21-55 years old. Willingness to participate in the study for a full year including multiple blood draws and PET-CT scanning Exclusion Criteria: Diabetes Use of systemic steroids Pregnancy or unwillingness to practice birth control of some kind through the PET-CT scanning period Recent vaccination for other reasons (e.g., traveler's vaccines) Significant intercurrent illness that might interfere with vaccination take or interpretation of PET-CT scanning (e.g., chemotherapy for cancer)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Natural Infection<br>previously naturally infected | Biological: FluShield<br>* Flu vaccine<br>Procedure: Blood Draws<br>* 50 cc of heparinized blood and 10 cc of serum at study entry and at 10-12 week post vaccination<br>Procedure: FDG PET-CT Scan<br>* PET scan<br>Genetic: Cytokine Profiling<br>* Blood draw for Cytokine Profiling Draw at 2,4 and 6 weeks post vaccination<br>|
| Active Comparator: FluShield - influenza positivity<br>prior FluShield ipsilateral vaccinated | Biological: FluShield<br>* Flu vaccine<br>Biological: FluShield - same arm<br>* Flu vaccine<br>Procedure: Blood Draws<br>* 50 cc of heparinized blood and 10 cc of serum at study entry and at 10-12 week post vaccination<br>Procedure: FDG PET-CT Scan<br>* PET scan<br>Genetic: Cytokine Profiling<br>* Blood draw for Cytokine Profiling Draw at 2,4 and 6 weeks post vaccination<br>|
| Active Comparator: FluShield - influenza positivity2<br>prior FluShield contralateral vaccinated | Biological: FluShield<br>* Flu vaccine<br>Biological: FluShield - opposite arm<br>* Flu vaccine<br>Procedure: Blood Draws<br>* 50 cc of heparinized blood and 10 cc of serum at study entry and at 10-12 week post vaccination<br>Procedure: FDG PET-CT Scan<br>* PET scan<br>Genetic: Cytokine Profiling<br>* Blood draw for Cytokine Profiling Draw at 2,4 and 6 weeks post vaccination<br>|
| Active Comparator: FluMist<br>prior FluMist vaccinated. | Biological: FluShield<br>* Flu vaccine<br>Procedure: Blood Draws<br>* 50 cc of heparinized blood and 10 cc of serum at study entry and at 10-12 week post vaccination<br>Procedure: FDG PET-CT Scan<br>* PET scan<br>Genetic: Cytokine Profiling<br>* Blood draw for Cytokine Profiling Draw at 2,4 and 6 weeks post vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET Scan AB Response | Natural infection but not ipsilateral IM injection of FluShield, will prime the host for a specific activation of spleen and bilateral lymph nodes following a subsequent i.m injection of FluShield, as detected by PET-CT performed 4-7 days post- FluShield immunization. | 4-7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, flu, vaccine, vaccination, immune response, FluShield, FluMist, PET-CT, Healthy Volunteers