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

This is a Phase IV 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 (A, B, C). 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 Group C 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.

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. Group C only: 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.