Protective Mechanisms Against a Pandemic Respiratory Virus (SLVP024)
Protective Mechanisms Against a Pandemic Respiratory Virus (SLVP024)
The purpose of the study is to investigate and compare the human immune response in
 epithelial cells of the nasopharyngeal mucosa and in blood to live, attenuated influenza
 vaccine (LAIV) in adults and in children.
The objective of the protocol is to investigate the human innate and adaptive immune
 responses in blood (only for adults) and nasopharyngeal mucosa resident cells to the live,
 attenuated influenza vaccine (LAIV) in both adults and children. The investigators hope to
 learn how the upper respiratory tract (URT) epithelial cells, the primary target of
 respiratory viruses, and the B cells and T cells, two major components of the immune system,
 respond to the influenza vaccine.

 The volunteers will be enrolled in two age groups:

 Group A: Up to 12 healthy non-twin volunteers, 2-8 years old, will be given seasonal LAIV.
 Each volunteer will complete a total of 3 visits. Volunteers will be divided in 2 sub-groups
 A-1 (n=6) and A-2 (n= 6) in order to collect nasopharyngeal swabs on different schedules (Day
 1 or Day 2). Volunteers will be assigned to these sub-groups based on convenience sampling.
 Both sub-groups will complete the Day 0 and Day 28 visits and one visit at either Day 1 or
 Day 2 post-immunization. Specimens will include nasopharyngeal swabs collected at Day 1 for
 Sub-group A1 and Day 2 for Sub-group A-2, and Day 28 for both sub-groups. No blood samples
 will be collected in this age group.

 Children with no prior influenza vaccine history will receive a second dose of vaccine (LAIV)
 at least 28 days after the first study dose, according to the ACIP guidelines.

 Group B: Up to 18 healthy non-twin volunteers, 18-49 yrs old, will be given seasonal LAIV
 vaccine. Each volunteer will complete a total of 5 visits. Volunteers will be divided into 3
 sub-groups B-1, B-2 and B-3 in order to collect nasopharyngeal swabs and blood specimens on
 different schedules (Day 0-6 hrs, Day 1 or Day 2). Volunteers will be assigned to these
 sub-groups based on convenience sampling. All sub-groups will complete visits at Day -7, Day
 0 pre-immunization, Day 7 and Day 28 and 1 additional time point: Sub-group B-1 at Day 0, 6
 hours post-immunization, Sub-group B-2 at Day 1 and Sub-group B-3 at Day 2. A nasopharyngeal
 swab will be collected at each visit except for Day 0 (baseline) and Day 7. A blood sample
 will be collected at each visit except Day -7
Inclusion Criteria:

 1. Otherwise healthy, ambulatory 2-8 years old (Group A) or 18-49 years old (Group B).

 2. Willing to complete the informed consent process (including assent for minors 7 years
 old and above).

 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 and exclusion criteria and vital
 signs.

 Exclusion Criteria:

 1. Prior off-study vaccination with the current 2012-2013 seasonal TIV or LAIV.

 2. Allergy to egg or egg products, or to vaccine components, including gentamicin,
 gelatin, arginine or MSG (LAIV)

 3. Life-threatening reactions to previous influenza vaccinations

 4. Asthma or history of wheezing

 5. Active systemic or serious concurrent illness, including febrile illness on the day of
 vaccination

 6. History of immunodeficiency (including HIV infection)

 7. Known or suspected impairment of immunologic function, including, but not limited to,
 clinically significant liver disease, diabetes mellitus treated with insulin, moderate
 to severe renal disease, or any other chronic disorder which, in the opinion of the
 investigator, might jeopardize volunteer safety or compliance with the protocol.

 8. Blood pressure >150 systolic or >95 diastolic at the first study visit and on the day
 of vaccination.

 9. Hospitalization in the past year for congestive heart failure or emphysema.

 10. Chronic Hepatitis B or C.

 11. Recent or current use of immunosuppressive medication, including systemic
 glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in
 all groups; inhaled steroid use is not permissible)

 12. Participants in close contact with anyone who has a severely weakened immune system
 should not receive LAIV

 13. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors
 such as breast cancer or prostate cancer with recurrence in the past year, and any
 hematologic cancer such as leukemia).

 14. Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive
 medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion
 of the investigator, might jeopardize volunteer safety or compliance with the
 protocol.

 15. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular
 medical follow up or hospitalization during the preceding year

 16. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet
 agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox must be
 reviewed by investigator to determine if this would affect the volunteer's safety.

 17. Receipt of blood or blood products within the past 6 months or planned used during the
 study.

 18. Medical or psychiatric condition or occupational responsibilities that preclude
 participant compliance with the protocol

 19. Receipt of Inactivated vaccine 14 days prior to study enrollment, or planned
 vaccinations prior to completion of last visit ( Day ~28 after study vaccination)

 20. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned
 vaccination prior to completion of last visit (Day ~28 after study vaccination)

 21. Need for allergy immunization (that cannot be postponed) during the study period.

 22. History of Guillain-Barré syndrome

 23. Pregnant or lactating woman (NA for children in Group A)

 24. Use of investigational agents within 30 days prior to enrollment or planned use during
 the study.

 25. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or
 planned donation prior to completion of the last visit.

 26. A current member of the clinical study team.

 27. Any condition which, in the opinion of the investigator, might interfere with
 volunteer safety, study objectives or the ability of the participant to understand or
 comply with the study protocol.