Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029)

Inclusion Criteria:

1. Otherwise healthy, 6 mo-49 year-old volunteers.
2. Willing to complete the informed consent process (including assent for minors 7-17 years of age).
3. Availability for follow-up for the planned duration of the study.
4. For parents of children 6 months - 4 years of age: Willing to participate in the study annually for up to 5 years (if yes, consider for annual return groups).
5. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.
6. Influenza vaccine-naive or only one prior season of flu immunization with IIV (does not apply to Groups F and G).

Exclusion Criteria:

1. Prior off-study vaccination with the current year's seasonal influenza vaccine
2. Receipt of LAIV in the prior season (does not apply to Groups F and G)
3. Received flu immunizations in 2 or more prior flu seasons (does not apply to Groups F and G)
4. Allergy to egg or egg products, or to vaccine components, (including gentamicin, gelatin, arginine or MSG if given LAIV4)
5. Life-threatening reactions to previous influenza vaccinations
6. Asthma in adults. Children aged 2 through 4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months, or for whom parents report that a health care provider stated that they had wheezing or asthma within the last 12 months \[If yes, not eligible for LAIV Groups A, B, C, \& F\].
7. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
8. History of immunodeficiency (including HIV infection)
9. For children or adolescents through 17 years of age,receiving aspirin therapy or aspirin-containing products \[If yes, not eligible for LAIV Groups A, B, C, and F\].
10. 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.
11. Blood pressure \>150 systolic or \>95 diastolic at first study visit and the day of vaccination (for children 12 yrs and older, and adults).
12. Hospitalization in the past year for congestive heart failure or emphysema.
13. Chronic Hepatitis B or C
14. 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)
15. Participants in close contact with anyone who has a severely weakened immune system and requires a protective environment. Exposure to such persons should be avoided for 7 days after receipt of LAIV. \[If yes, may be ineligible for Groups A,B, C and F\].
16. 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).
17. 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
18. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
19. 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.
20. Has taken an influenza antiviral medication within 48 hours prior to study vaccination \[If yes, not eligible for LAIV Groups A, B, C and F\].
21. Receipt of blood or blood products within the past 6 months or planned used during the study
22. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol.
23. Receipt of inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit
24. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit
25. Need for allergy immunization (that cannot be postponed) during the study period
26. History of Guillain-Barre syndrome
27. Pregnant woman
28. Breastfeeding \[If yes, not eligible for LAIV Group F\]
29. Use of investigational agents within 30 days prior to enrollment or planned use during the study
30. 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
31. 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.