Functional Consequences of T-bet Expression in Flu-specific Memory B Cells After Live Attenuated Influenza Vaccine (LAIV)

Study Overview
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Brief Summary
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As yet the investigators do not understand if there are biomarkers of immune protection after the Flumist or Live Attenuated Flu Vaccine (LAIV). Here the investigators test the hypothesis that the T-bet expressing fraction of flu-specific B cells after live attenuated influenza vaccination also serves as an early biomarker of long-lived antibody responses after vaccination. In this study the investigators will be providing the LAIV to up to 10 healthy subjects and assaying their immune response and then providing the intramuscular influenza vaccination and testing to see if the immune protection after the LAIV also protects after the intramuscular influenza vaccination. Update: We have amended this protocol to study the antigen-specific B cell populations that circulate after LAIV or IIV prime and LAIV or IIV boost.

Detailed Description
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Previously (1) the investigators established that a fluorochrome labeled reagent with the influenza antigen hemagglutinin accurately identified flu-specific B cells after inactivated influenza vaccination and we established that a subset of these flu-specfiic B cells that express the lineage defining master transcriptional regulator, T-bet, correlate with long lived antibody responses. As yet the investigators do not understand if there are biomarkers of immune protection after the Flumist or Live Attenuated Flu Vaccine (LAIV). Here the investigators test the hypothesis that the T-bet expressing fraction of flu-specific B cells after live attenuated influenza vaccination also serves as an early biomarker of long-lived antibody responses after vaccination. In this study the investigators will be providing the LAIV to up to 10 healthy subjects and assaying their immune response and then providing the intramuscular influenza vaccination and testing to see if the immune protection after the LAIV also protects after the intramuscular influenza vaccination. Update: We have amended this protocol to study the antigen-specific B cell populations that circulate after LAIV or IIV prime and LAIV or IIV boost.

Official Title
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Functional Consequences of T-bet Expression in Flu-specific Memory B Cells After Live Attenuated Influenza Vaccine (LAIV)

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Treatment Group Live Attenuated Flu Vaccine (LAIV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Missed getting the flu vaccine in the last year No history of reactive airway disease No history of allergy to LAIV No history of allergy to IIV Self-identify as healthy without an immunocompromising condition defined as cancer, autoimmune disease, organ transplant or receipt of steroids. Exclusion Criteria: History of reactive airway disease History of allergy to LAIV or IIV Do not self-identify as healthy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br> | Biological: Treatment Group Live Attenuated Flu Vaccine (LAIV)<br>* We will administer LAIV once as a vaccine prime and IIV once as a vaccine boost with serial weekly blood draws for a month to validate a biomarker of LAIV efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome Measure: Participants with a positive T-bet expressing Flu-specific B cell subtype | The investigators will perform a blood test on lymphocytes from circulating blood. | Baseline | 
| Outcome Measure: Participants with a positive T-bet expressing Flu-specific B cell subtype | The investigators will perform a blood test on lymphocytes from circulating blood. | 7 days post first injection | 
| Outcome Measure: Participants with a positive T-bet expressing Flu-specific B cell subtype | The investigators will perform a blood test on lymphocytes from circulating blood. | 14 days post first injection | 
| Outcome Measure: Participants with a positive T-bet expressing Flu-specific B cell subtype | The investigators will perform a blood test on lymphocytes from circulating blood. | 7 days post second injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Influenza, Efficacy