The Role of CD4+ Memory Phenotype, Memory, and Effector T Cells in Vaccination and Infection

The purpose of this study is provide a better understanding of the adaptive immune response to the licensed influenza vaccines in children.

This is a Phase I study of up to 100 healthy children, ages 6 months to 10 years of age, who will receive either Flumist® live, attenuated influenza virus vaccine, quadrivalent (LAIV4) or the current Fluzone® inactivated influenza vaccine, quadrivalent (IIV4). The volunteers will be enrolled into one of 3 Groups. Volunteers will return each year until 2018-2019 for annual flu immunizations and study visits. Questionnaires will be administered annually to record demographic characteristics, vaccination history, exposure to animals, day care and medically attended illness. There are no exclusions for gender, ethnicity or race.

Volunteers in the Non-twin Flu/MMRV naive group will also receive the measles, mumps, rubella and varicella (MMRV) vaccine at approximately 12-15 months of age (to be administered by the volunteers' personal pediatrician, not as a study vaccine). They will then come for a study visit to collect blood 60 days later.

Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs.

Eligibility Criteria:
Inclusion Criteria:

1. Otherwise healthy non-twins 6 months - 10 years old, or 2-5 year old identical (MZ) twins.
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 - annually until 2018-2019 influenza vaccination season
4. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.
5. Non-twin flu/MMRV naive group: Willing to have primary care physician immunize child with the MMRV vaccine and return for a study visit approximately 60 days later.

Exclusion Criteria:

1. Prior off-study vaccination with the current year's seasonal influenza vaccine.
2. Life-threatening reactions to previous influenza vaccinations
3. Allergy to egg or egg products, or to vaccine components
4. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
5. History of immunodeficiency (including HIV infection)
6. 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.
7. Chronic Hepatitis B or C.
8. 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)
9. Malignancy
10. 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.
11. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
12. Receipt of blood or blood products within the past 6 months or planned used during the study.
13. Receipt of Inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit ( \~ 28 Day after study vaccination)
14. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (\~ 28 Day after study vaccination)
15. Need for allergy immunization (that cannot be postponed) during the study period.
16. History of Guillain-Barré syndrome
17. Use of investigational agents within 30 days prior to enrollment or planned use during the study.
18. 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.
19. 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.