Study of Seasonal Influenza Vaccine Against H5N1 Avian Influenza Virus

Study Overview
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Brief Summary
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This will be a randomized, open-label, pilot feasibility study of four 2-dose vaccine regimens in healthy volunteers using two commercially available seasonal influenza vaccines to compare immune responses and in vitro cross-reactivity against H5N1. Vaccine doses will be spaced by approximately 8 weeks to allow for optimal prime boost conditions. Humoral, cellular and secretory immune responses will be measured 2 and 4 weeks after each vaccine dose and compared with baseline values.

Official Title
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Evaluation of In Vitro Cross-Reactivity With Avian Influenza H5N1 Virus in Healthy Volunteers Vaccinated With a Prime Boost Regimen of Seasonal Influenza Vaccine

Conditions
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Influenza

Intervention / Treatment
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* Biological: FluMist® live, attenuated, intranasal seasonal influenza vaccine
* Biological: Fluzone® inactivated influenza virus vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-49 years. Healthy as determined by the PI or designate Willing to give informed consent. Willing to attend follow-up appointments and undergo study procedures. US passport holder residing in Bangkok If military, have a letter of approval for participation from the chain of command (Unit Commander). Exclusion Criteria: History of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine. Severe or life-threatening reaction to any previous vaccine. History of chronic respiratory illness, including asthma and sinusitis. History of heart disease History of kidney disease Metabolic disease such as diabetes Immunocompromised as determined by the PI, or a household contact of an immunocompromised individual. History of Guillain-Barre syndrome. Blood disease including sickle cell disease and/or bleeding tendency (by history or based on medical records). Any influenza vaccination within the previous 6 months, or any other vaccine within 30 days of either dose of influenza vaccine. Pregnant woman or nursing mother or unwilling to use reliable contraception during the study period until the final day of follow-up. Blood donation within the preceding 3 months, or screening hemoglobin value of <12.5 g/dl. Receipt of blood products including immunoglobulins within the preceding 3 months. Receiving any of the following therapies: aspirin, warfarin, theophylline, phenytoin, aminopyrine, immunosuppressive drugs, Receipt of any antiviral agents within 48 hours of vaccine administration. HIV positive on screening blood tests. Any other condition that in the opinion of the study investigator warrants exclusion from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Autologous prime boost regimen 1<br>FluMist® live intranasal vaccine (LAIV) 0.2mL (0.1mL per nostril): 2 doses separated by 8 weeks (+/- 7 days) | Biological: FluMist® live, attenuated, intranasal seasonal influenza vaccine<br>* FluMist® live, attenuated, intranasal seasonal influenza vaccine 0.2mL (0.1mL per nostril)<br>|
| Active Comparator: Autologous prime boost regimen 2<br>Fluzone® inactivated seasonal influenza virus vaccine intramuscularly: 2 doses separated by 8 weeks (+7 days) | Biological: Fluzone® inactivated influenza virus vaccine<br>* Fluzone® inactivated influenza virus vaccine 0.5mL intramuscularly<br>|
| Experimental: Heterologous prime boost regimen 1<br>FluMist® live, intranasal vaccine single dose, followed by Fluzone® inactivated influenza virus vaccine 8 weeks (+/-7 days) later | Biological: FluMist® live, attenuated, intranasal seasonal influenza vaccine<br>* FluMist® live, attenuated, intranasal seasonal influenza vaccine 0.2mL (0.1mL per nostril)<br>Biological: Fluzone® inactivated influenza virus vaccine<br>* Fluzone® inactivated influenza virus vaccine 0.5mL intramuscularly<br>|
| Experimental: Heterologous prime boost regimen 2<br>Fluzone® inactivated seasonal influenza virus vaccine single dose, followed by FluMist® live, intranasal seasonal influenza vaccine 0.2mL 8 weeks (+/- 7 days) later | Biological: FluMist® live, attenuated, intranasal seasonal influenza vaccine<br>* FluMist® live, attenuated, intranasal seasonal influenza vaccine 0.2mL (0.1mL per nostril)<br>Biological: Fluzone® inactivated influenza virus vaccine<br>* Fluzone® inactivated influenza virus vaccine 0.5mL intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antibody titers |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of 2 doses of seasonal influenza vaccine in healthy adults |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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seasonal influenza vaccine, avian influenza H5N1, cross reactivity, prime boost